Cell Division and Cancer Biology PDF

College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City...

College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Week 4-5: Unit Learning Outcomes (ULO): At the end of the unit, you are expected to: a. Describe each phase of mitosis and meiosis; and b. describe how a cell can be transformed into a cancer cell, and the unusual features of cancer cells. Big Picture in Focus: ULOa: Describe each phase of mitosis and meiosis Metalanguage In this section, the essential terms relevant to the study of cell division and to demonstrate ULOa will be operationally defined to establish a common frame of reference as to how the texts work. You will encounter these terms as we go through the study of the nature of mathematics. Please refer to these definitions in case you will encounter difficulty in understanding some concepts. 1. Mitosis - Cell division that results in two daughter cells each having the same number and kind of chromosomes as the parent nucleus, 2. Meiosis - Cell division that results in four daughter cells each with half the number of chromosomes of the parent cell, as in the production of gametes 3. Cyclins - Proteins associated with the cycle of cell division which are thought to initiate certain processes of mitosis. 4. Interphase - The longest stage in the eukaryote cell cycle. During interphase, the cell acquires nutrients, creates and uses proteins and other molecules, and starts the process of cell division by replicating the DNA. 5. Cytokinesis - The cytoplasmic division of a cell at the end of mitosis or meiosis, bringing about the separation into two daughter cells. 6. Haploid - Having a single set of unpaired chromosomes. Example: egg cell and sperm cell. 7. Nondisjunction - Nondisjunction is the failure of paired chromosomes to separate during cell division, which makes both chromosomes go to one daughter cell and none go to the other. Essential Knowledge Cell Division and Reproduction Sometimes you accidentally bite your lip or skin your knee, but in a matter of days the wound heals. Is it magic? Or, is there another explanation? 41 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Every day, every hour, every second one of the most important events in life is going on in your body—cells are dividing. When cells divide, they make new cells. A single cell divides to make two cells and these two cells then divide to make four cells, and so on. We call this process "cell division" and "cell reproduction," because new cells are formed when old cells divide. The ability of cells to divide is unique for living organisms. Figure 15: A 3D image of a mouse cell in the final Why Do Cells Divide? stages of cell division. https://images.app.goo.gl/uRVDJmvum2vE5NH78 Cells divide for many reasons. For example, when you skin your knee, cells divide to replace old, dead, or damaged cells. Cells also divide so living things can grow. When organisms grow, it isn't because cells are getting larger. Organisms grow because cells are dividing to produce more and more cells. In human bodies, nearly two trillion cells divide every day. How Do Cells Know When to Divide? In cell division, the cell that is dividing is called the "parent" cell. The parent cell divides into two "daughter" cells. The process then repeats in what is called the cell cycle. Cells regulate their division by communicating with each other using chemical signals from special proteins called cyclins. These signals act like switches to tell cells when to start dividing and later when to stop dividing. It is important for cells to divide so you can grow and so your cuts heal. It is also important for cells to stop dividing at the right time. If a cell cannot stop dividing when it is supposed to stop, this can lead to a disease called cancer. Some cells, like skin cells, are constantly dividing. We need to continuously make new skin cells to replace the skin cells we lose. Did you know we lose 30,000 to 40,000 dead skin cells every minute? That means we lose around 50 million cells every day. This is a lot of skin cells to replace, making cell division in skin cells is so important. Other cells, like nerve and brain cells, divide much less often. How do cells divide? There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division”, they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells. Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result. 42 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing. Mitosis involves the division of body cells, while meiosis involves the division of sex cells. The division of a cell occurs once in mitosis but twice in meiosis. Two daughter cells are produced after mitosis and cytoplasmic division, while four daughter cells are produced after meiosis. Mitosis is a way of making more cells that are genetically the same as the parent cell. It plays an important part in the development of embryos, and it is important for the growth and development of our bodies as well. Mitosis produces new cells, and replaces cells that are old, lost or damaged. All cells in the body undergo mitosis except the sex cells which undergo the other process called meiosis. Before mitosis starts, the cell must undergo an initial stage called Interphase. In interphase, the cell is engaged in metabolic activity and performing its preparation for mitosis (the next four phases that lead up to and include nuclear division). It is also where the DNA of each chromosome replicates. Interphase is often included in discussions of mitosis, but interphase is technically not part of mitosis, but rather encompasses stages G1, S, and G2 of the cell cycle. Figure 16: Stages of Interphase https://images.app.goo.gl/Ukv4hRcN9X36FPY66 Each chromosome then reorganizes into paired structures called sister chromatids, with each member of the pair containing a full copy of the DNA sequence. Mitosis occurs in four stages: 43 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 1. Prophase: Chromatin in the nucleus begins to condense and becomes visible in the light microscope as chromosomes. The nucleolus disappears. Centrioles begin moving to opposite ends of the cell and fibers extend from the centromeres. Some fibers cross the cell to form the mitotic spindle. Figure 17: Prophase http://www.biology.arizona.edu /cell_bio/tutorials/cell_cycle/gr aphics/interphaseB.gif 2. Metaphase: Spindle fibers align the chromosomes along the middle of the cell nucleus. This line is referred to as the metaphase plate. This organization helps to ensure that in the next phase, when the chromosomes are separated, each new nucleus will receive one copy of each chromosome. Figure 18: Metaphase http://www.biology.arizona.edu /cell_bio/tutorials/cell_cycle/gr aphics/interphaseB.gif 3. Anaphase: The paired chromosomes separate at the kinetochores and move to opposite sides of the cell. Motion results from a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules. Figure 19: Anaphase http://www.biology.arizona.edu /cell_bio/tutorials/cell_cycle/gr aphics/interphaseB.gif 4. Telophase: Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei. The chromosomes disperse and are no longer visible under the light microscope. The spindle fibers disperse, and cytokinesis or the partitioning of the cell may also begin during this stage. Figure 20: Telophase http://www.biology.arizona.ed u/cell_bio/tutorials/cell_cycle/ graphics/interphaseB.gif 44 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Figure 21: Stages of Mitosis https://images.app.goo.gl/6n1VCcwudCJGVwTG7 Cytokinesis The first visible change of cytokinesis in an animal cell is the sudden appearance of a pucker, or cleavage furrow, on the cell surface. The furrow rapidly deepens and spreads around the cell until it completely divides the cell in two. In plant cells, the rigid wall requires that a cell plate be synthesized between the two daughter cells. Figure 22: Cytokinesis differs in animal and plant cells https://images.app.goo.gl/neKecCkuivqcE5q56 Meiosis is a process where a single cell divides twice to produce four cells containing half the original amount of genetic information. These cells are our sex cells – sperm in males, eggs in females. During meiosis, one cell divides, replicates and divides again for the second time to form four daughter cells. These four daughter cells only have half the number of chromosomes of the parent cell – they are haploid. Meiosis produces our sex cells or gametes (eggs in females and sperm in males). Meiosis can be divided into nine stages. These are divided between the first time the cell divides meiosis I and the second time it divides meiosis II: Meiosis I 1. Interphase: The DNA in the cell is copied resulting in two identical full sets of chromosomes. 45 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Outside of the nucleus are two centrosomes, each containing a pair of centrioles, these structures are critical for the process of cell division. During interphase, microtubules extend from these centrosomes. 2. Prophase I: The copied chromosomes condense into X-shaped structures that can be easily seen under a microscope. Each chromosome is composed of two sister chromatids containing identical genetic information. The chromosomes pair up so that both copies of chromosome 1 are together, both copies of chromosome 2 are together, and so on. The pairs of chromosomes may then exchange bits of DNA in a process called recombination or crossing over. At the end of Prophase I the membrane around the nucleus in the cell dissolves away, releasing the chromosomes. The meiotic spindle, consisting of microtubules and other proteins, extends across the cell between the centrioles. 3. Metaphase I: The chromosome pairs line up next to each other along the center (equator) of the cell. The centrioles are now at opposites poles of the cell with the meiotic spindles extending from them. The meiotic spindle fibers attach to one chromosome of each pair. 4. Anaphase I: The pair of chromosomes are then pulled apart by the meiotic spindle, which pulls one chromosome to one pole of the cell and the other chromosome to the opposite pole. In meiosis I the sister chromatids stay together. This is different to what happens in mitosis and meiosis II. 5. Telophase I and cytokinesis: The chromosomes complete their move to the opposite poles of the cell. At each pole of the cell a full set of chromosomes gather together. A membrane forms around each set of chromosomes to create two new nuclei. The single cell then pinches in the middle to form two separate daughter cells each containing a full set of chromosomes within a nucleus. This process is known as cytokinesis. Meiosis II 6. Prophase II: Now there are two daughter cells, each with 23 chromosomes (23 pairs of chromatids). In each of the two daughter cells the chromosomes condense again into visible X-shaped structures that can be easily seen under a microscope. The membrane around the nucleus in each daughter cell dissolves away releasing the chromosomes. The centrioles duplicate. The meiotic spindle forms again. 7. Metaphase II: In each of the two daughter cells the chromosomes (pair of sister chromatids) line up end- to-end along the equator of the cell. The centrioles are now at opposites poles in each of the daughter cells. Meiotic spindle fibers at each pole of the cell attach to each of the sister chromatids. 46 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 8. Anaphase II: The sister chromatids are then pulled to opposite poles due to the action of the meiotic spindle. The separated chromatids are now individual chromosomes. 9. Telophase II and cytokinesis: The chromosomes complete their move to the opposite poles of the cell. At each pole of the cell a full set of chromosomes gather together. A membrane forms around each set of chromosomes to create two new cell nuclei. This is the last phase of meiosis; however, cell division is not complete without another round of cytokinesis. Once cytokinesis is complete there are four granddaughter cells, each with half a set of chromosomes (haploid): in males, these four cells are all sperm cells in females, one of the cells is an egg cell while the other three are polar bodies (small cells that do not develop into eggs). 47 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 DIPLOID HAPLOID Figure 23: Stages of Meiosis 48 | P a ghttps://images.app.goo.gl/coFqRwak7snWdCh96 e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Nondisjunction Nondisjunction is the failure of paired chromosomes to separate during cell division, which makes both chromosomes go to one daughter cell and none go to the other. Nondisjunction causes errors in chromosome number, such as trisomy 21 (Down syndrome) and monosomy X (Turner syndrome). It is also a common cause of early spontaneous abortions. Figure 24: Normal and Abnormal Cell Divisions https://images.app.goo.gl/PRB5XDzHy32MCxRP9 Self-Help You can also refer to the sources below to help you further understand the lesson: 1) Klug, W. et al. (2016). Concepts of genetics. London: Pearson Education Limited. 2) Belk, C. & Maier, V. (2016). Biology: Science for life. 5th ed. London: Pearson Education Limited. Let’s Check Activity 4. Let us try to check your understanding of the discussion. Read the questions carefully. Encircle the letter that corresponds to the correct answer. 1. Which sequence is correctly arranged? a. G1-S-G2-mitosis-cytokinesis c. mitosis-G1-G2-S-cytokinesis b. G1-G2-S-cytokinesis-mitosis d. cytokinesis-G1-S-G2-mitosis 2.The following can undergo mitosis, EXCEPT: a. muscle cell b. skin cell c. sperm cell d. bone cell For items 3-5, choose from the following options: a. prophase b. telophase c. metaphase d. anaphase prophase 3. The nuclear membrane of a cell disintegrates in this stage telophase 4. The nuclear membrane reappears in this stage anaphase 5. Spindle fibers pull one set of chromosomes to each pole in this stage 6. Cells undergo division for the following reasons, EXCEPT: a. repair b. growth c. death d. reproduction 49 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 7. How many times does a cell undergoing meiosis replicate? a. 1 b. 2 c. 3 d. 23 MITOSIS - 1 8. How many times does a cell undergoing meiosis divide? a. 1 b. 2 c. 3 d. 23 MITOSIS - 1 9. How many sperm cells are produced in one meiotic cycle? a. 1 b. 2 c. 3 d. 4 MITOSIS - 1 10. Among the cells produced through meiosis in females, 3 out of 4 would become a. egg cells b. polar bodies c. bacteria d. white blood cells Let’s Analyze Activity 4. In this activity, elaborate your answer to each of the questions below: 1. Why do cells need to undergo cell division? Cells need to undergo cell division for growth, allowing organisms to increase in size and develop. It is also essential for repair and replacing damaged or worn-out cells to maintain proper function. Additionally, cell division enables reproduction, either for asexual reproduction in single-celled organisms or the production of gametes for sexual reproduction in multicellular organisms. 2. Why do sex cells need to be haploids (half a set of chromosomes)? Sex cells need to be haploids to ensure that when they combine during fertilization, the resulting offspring has the correct number of chromosomes. If sex cells were diploid (with two sets of chromosomes), the fertilized egg would end up with double the normal number of chromosomes. By being haploid, each sex cell contributes half of the genetic material, maintaining the stability of the species' chromosome number across generations. 3. Differentiate cytokinesis in plant and animal cells. Cytokinesis in animal cells occurs through a process called cleavage, where the cell membrane pinches inward, forming a cleavage furrow that eventually divides the cell into two. In plant cells, cytokinesis involves the formation of a new cell wall called the "cell plate" that develops in the middle of the cell, eventually separating the two daughter cells. The key difference is that plant cells cannot pinch in their membrane due to the rigid cell wall, so they form a new structure to divide the cells. 50 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 In a Nutshell Activity 4. Based from the definition of the most essential terms and concepts in the study of the phases of mitosis and meiosis and the learning exercises that you have done, please feel free to write your arguments or lessons learned below. 1. 2. 3. Q&A List Do you have any question for clarification? Questions/Issues Answers 1. 2. 3. 4. 5. Keywords Index mitosis meiosis cyclins interphase cytokinesis haploid nondisjunction 51 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Big Picture in Focus: ULOb: describe how a cell can be transformed into a cancer cell, and the unusual features of cancer cells. Metalanguage In this section, the essential terms relevant to the study of cancer cells and their effects; and to demonstrate ULOb will be operationally defined to establish a common frame of reference as to how the texts work. You will encounter these terms as we go through the study of the nature of mathematics. Please refer to these definitions in case you will encounter difficulty in understanding some concepts. 1. Cancer - A disease caused by an uncontrolled division of abnormal cells in a part of the body. 2. Apoptosis - The death of cells which occurs as a normal and controlled part of an organism's growth or development. 3. Metastasis - The process by which cancer spreads from the place at which it first arose as a primary tumor to distant locations in the body. 4. Mutation - Occurs when a DNA gene is damaged or changed in such a way as to alter the genetic message carried by that gene. 5. Mutagen - An agent, such as radiation or a chemical substance, which causes genetic mutation. 6. Carcinogen - Any substance or agent that causes cancer. 7. Benign - Refers to a condition, tumor, or growth that is not cancerous. 8. Malignant – Refers to a tumor which is made of cancer cells, and can invade nearby tissues. Essential Knowledge Cancer cells are cells gone wrong — in other words, they no longer respond to many of the signals that control cellular growth and death. Cancer cells originate within tissues and, as they grow and divide, they diverge ever further from normalcy. Over time, these cells become increasingly resistant to the controls that maintain normal tissue — and as a result, they divide more rapidly than their progenitors and become less dependent on signals from other cells. Cancer cells even evade programmed cell death, despite the fact that their multiple abnormalities would normally make them prime targets for apoptosis. In the late stages of cancer, cells break through normal tissue boundaries and metastasize (spread) to new sites in the body. How Do Cancer Cells Differ from Normal Cells? In normal cells, hundreds of genes intricately control the process of cell division. Normal growth requires a balance between the activity of those genes that promote cell proliferation and those that suppress it. It also relies on the activities of genes that signal when damaged cells should undergo apoptosis. 52 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Cells become cancerous after mutations accumulate in the various genes that control cell proliferation. According to research findings from the Cancer Genome Project, most cancer cells possess 60 or more mutations. The challenge for medical researchers is to identify which of these mutations are responsible for particular kinds of cancer. This process is akin to searching for the proverbial needle in a haystack, because many of the mutations present in these cells have little to nothing to do with cancer growth. Different kinds of cancers have different mutational signatures. However, scientific comparison of multiple tumor types has revealed that certain genes are mutated in cancer cells more often than others. For instance, growth-promoting genes, such as the gene for the signaling protein Ras, are among those most commonly mutated in cancer cells, becoming super-active and producing cells that are too strongly stimulated by growth receptors. Some chemotherapy drugs work to counteract these mutations by blocking the action of growth-signaling proteins. The breast cancer drug Herceptin, for example, blocks overactive receptor tyrosine kinases (RTKs), and the drug Gleevec blocks a mutant signaling kinase associated with chronic myelogenous leukemia. Other cancer-related mutations inactivate the genes that suppress cell proliferation or those that signal the need for apoptosis. These genes, known as tumor suppressor genes, normally function like brakes on proliferation, and both copies within a cell must be mutated in order for uncontrolled division to occur. For example, many cancer cells carry two mutant copies of the gene that codes for p53, a multifunctional protein that normally senses DNA damage and acts as a transcription factor for checkpoint control genes. What Causes Cancer? Cancer is caused by accumulated damage to genes. Such changes may be due to chance or to exposure to a cancer-causing substance. The substances that cause cancer are called carcinogens. A carcinogen may be a chemical substance, such as certain molecules in tobacco smoke. The cause of cancer may be environmental agents, viral or genetic factors. We should bear in mind, though, that in the majority of cancer cases we cannot attribute the disease to a single cause. We can roughly divide cancer risk factors into the following groups: 1. Biological or internal factors, such as age, gender, inherited genetic defects and skin type 2. Environmental exposure, for instance to radon and UV radiation, and fine particulate matter 3. Occupational risk factors, including carcinogens such as many chemicals, radioactive materials and asbestos 4. Lifestyle-related factors. Lifestyle-related factors that cause cancer include: tobacco alcohol UV radiation in sunlight some food-related factors, such as nitrites and poly aromatic hydrocarbons generated by barbecuing food). 53 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 Cancer causing factors related to work and living environments include: asbestos fibers tar and pitch polynuclear hydrocarbons (e.g. benzopyrene) Some metal compounds Some plastic chemicals (e.g. Vinyl chloride) Bacteria and viruses can cause cancer: Helicobacter pylori (H. pylori, which causes gastritis) HBV, HCV (hepatitis viruses that cause hepatitis) HPV (human papilloma virus, papilloma virus, which causes changes e.g. Cervical cells) EBV (Epstein-Barr virus, the herpes virus that causes inflammation of the throat lymphoid) Radiation can cause cancer: ionizing radiation (e.g. X-ray radiation, soil radon) non-ionized radiation (the sun’s ultraviolet radiation) Some drugs may increase the risk of cancer: certain antineoplastic agents certain hormones medicines that cause immune deficiency Figure 25: Microevolution of a cancer cell https://images.app.goo.gl/oPgb3K861UKfDzW2A How Do Cancerous Changes Arise? Gene mutations accumulate over time as a result of independent events. Consequently, the path to cancer involves multiple steps. In fact, many scientists view the progression of cancer as a microevolutionary process. To understand what this means, consider the following: When a mutation gives a cancer cell a growth advantage, it can make more copies of itself than a normal cell can — and its offspring can outperform their noncancerous counterparts in the competition for resources. Later, a second mutation might provide the cancer cell with yet another reproductive advantage, which in turn intensifies its competitive advantage even more. And, if key checkpoints are missed or repair genes are damaged, then the rate of damage accumulation increases still further. This process continues with every new mutation that offers such benefits, and it is a driving force in the evolution of living things — not just cancer cells. 54 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 How Do Cancer Cells Spread to Other Tissues? During the early stages of cancer, tumors are typically benign and remain confined within the normal boundaries of a tissue. As tumors grow and become malignant, however, they gain the ability to break through these boundaries and invade adjoining tissues. Invasive cancer cells often secrete proteases that enable them to degrade the extracellular matrix at a tissue's boundary. Proteases also give cancer cells the ability to create new passageways in tissues. For example, they can break down the junctions that join cells together, thereby gaining access to new territories. Metastasis — literally meaning new place — is one of the terminal stages of cancer. In this stage, cancerous cells enter the bloodstream or the lymphatic system and travel to a new location in the body, where they begin to divide and lay the foundation for secondary tumors. Not all cancer cells can metastasize. In order to spread in this way, the cells must have the ability to penetrate the normal barriers of the body so that they can both enter and exit the blood or lymph vessels. Even traveling metastatic cancer cells face challenges when trying to grow in new areas. Figure 26: The difference between normal cells and cancer cells https://images.app.goo.gl/P5xicT22jou6K8K3A Cancer is a collective name for many different diseases caused by a common mechanism: uncontrolled cell division. Despite the redundancy and overlapping levels of cell-cycle control, errors occur. One of the critical processes monitored by the cell-cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. Even when all of the cell-cycle controls are fully functional, a small percentage of replication errors (mutations) will be passed on to the daughter cells. If one of these changes to the DNA nucleotide sequence occurs within a gene, a gene mutation results. All cancers begin when a gene mutation gives rise to a faulty protein that participates in the process of cell reproduction. The change in the cell that results from the malformed protein may be minor. Even minor mistakes, however, may allow subsequent mistakes to occur more readily. Over 55 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 and over, small, uncorrected errors are passed from parent cell to daughter cells and accumulate as each generation of cells produces more non-functional proteins from uncorrected DNA damage. Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. Uncontrolled growth of the mutated cells outpaces the growth of normal cells in the area, and a tumor can result. Proto-oncogenes The genes that code for the positive cell-cycle regulators are called proto-oncogenes. Proto- oncogenes are normal genes that, when mutated, become oncogenes—genes that cause a cell to become cancerous. Consider what might happen to the cell cycle in a cell with a recently acquired oncogene. In most instances, the alteration of the DNA sequence will result in a less functional (or non-functional) protein. The result is detrimental to the cell and will likely prevent the cell from completing the cell cycle; however, the organism is not harmed because the mutation will not be carried forward. If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. For example, a mutation that allows Cdk, a protein involved in cell-cycle regulation, to be activated before it should be could push the cell cycle past a checkpoint before all of the required conditions are met. If the resulting daughter cells are too damaged to undertake further cell divisions, the mutation would not be propagated and no harm comes to the organism. However, if the atypical daughter cells are able to divide further, the subsequent generation of cells will likely accumulate even more mutations, some possibly in additional genes that regulate the cell cycle. The Cdk example is only one of many genes that are considered proto-oncogenes. In addition to the cell-cycle regulatory proteins, any protein that influences the cycle can be altered in such a way as to override cell-cycle checkpoints. Once a proto-oncogene has been altered such that there is an increase in the rate of the cell cycle, it is then called an oncogene. Tumor Suppressor Genes Like proto-oncogenes, many of the negative cell-cycle regulatory proteins were discovered in cells that had become cancerous. Tumor suppressor genes are genes that code for the negative regulator proteins, the type of regulator that—when activated—can prevent the cell from undergoing uncontrolled division. The collective function of the best-understood tumor suppressor gene proteins, retinoblastoma protein (RB1), p53, and p21, is to put up a roadblock to cell-cycle progress until certain events are completed. A cell that carries a mutated form of a negative regulator might not be able to halt the cell cycle if there is a problem. Mutated p53 genes have been identified in more than half of all human tumor cells. This discovery is not surprising in light of the multiple roles that the p53 protein plays at the G1 checkpoint. The p53 protein activates other genes whose products halt the cell cycle (allowing time for DNA repair), activates genes whose products participate in DNA repair, or activates genes that initiate cell death when DNA damage cannot be repaired. A damaged p53 gene can result in the cell behaving as if there are no mutations (Figure 6.8). This allows cells to divide, propagating the mutation in daughter 56 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 cells and allowing the accumulation of new mutations. In addition, the damaged version of p53 found in cancer cells cannot trigger cell death. Figure 27: How a normal and abnormal p53 behaves https://images.app.goo.gl/3uwjuWu2ACWyXgAo8 Is It Possible to Prevent Cancer? Most experts are convinced that many cancers can either be prevented or the risk of developing cancers can be markedly reduced. Some of the cancer prevention methods are simple; others are relatively extreme, depending on an individual's view. Cancer prevention, by avoiding its potential causes, is the simplest method. First on most clinicians and researchers list is to stop (or better, never start) smoking tobacco. Avoiding excess sunlight (by decreasing exposure or applying sunscreen) and many of the chemicals and toxins are excellent ways to avoid cancers. Avoiding contact with certain viruses and other pathogens also are likely to prevent some cancers. People who have to work close to cancer-causing agents (chemical workers, X-ray technicians, ionizing radiation researchers, asbestos workers) should follow all safety precautions and minimize any exposure to such compounds. Although the FDA and the CDC suggests that there is no scientific evidence that definitively says cell phones cause cancer, other agencies call for more research or indicate the risk is very low. Individuals who are concerned can limit exposure to cell phones by using an earpiece and simply make as few cellphone calls as possible. There are two vaccines currently approved by the U.S. Food and Drug Administration (FDA) to prevent specific types of cancer. Vaccines against the hepatitis B virus, which is considered a cause of some liver cancers, and vaccines against human papillomavirus (HPV) types 16 and 18 are available. According to the NCI, these viruses are responsible for about 70% of cervical cancers. These viruses also plays a role in cancers arising in the head and neck, as well as cancers in the anal 57 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 region, and probably in others. Today, vaccination against HPV is recommended in teenagers and young adults of both sexes. The HPV virus is so common that by the age of 50, half or more people have evidence of being exposed to it. Sipuleucel-T is a new vaccine approved by the FDA to help treat advanced prostate cancer. Although vaccine does not cure prostate cancer, it has been shown to help extend the lifespan of individuals with advanced prostate cancer. People with a genetic predisposition to develop certain cancers and others with a history of cancers in their genetically linked relatives currently cannot change their genetic makeup. However, some individuals who have a high possibility of developing genetically linked cancer have taken actions to prevent cancer development. For example, some young women who have had many family members develop breast cancer have elected to have their breast tissue removed even if they have no symptoms or signs of cancer development to reduce or eliminate the possibility that they will develop breast cancer. Some doctors consider this as an extreme measure to prevent cancer while others do not. Screening tests and studies for cancer are meant to help detect a cancer at an early stage when the cancer is more likely to be potentially cured with treatment. Such screening studies are breast exams, testicular exams, colon-rectal exams (colonoscopy), mammography, certain blood tests, prostate exams, urine tests and others. People who have any suspicion that they may have cancer should discuss their concerns with their doctor as soon as possible. Screening recommendations have been the subject of numerous conflicting reports in recent years. Screening may not be cost effective for many groups of patients or lead to unnecessary further invasive tests, but individual patients' unique circumstances should always be considered by doctors in making recommendations about ordering or not ordering screening tests. Self-Help You can also refer to the sources below to help you further understand the lesson: 1) Klug, W. et al. (2016). Concepts of genetics. London: Pearson Education Limited. 2) Belk, C. & Maier, V. (2016). Biology: Science for life. 5th ed. London: Pearson Education Limited. Let’s Check Activity 5. Let us try to check your understanding of the discussion. Read the questions carefully. Encircle the letter that corresponds to the correct answer. 1. A gene that codes for a protein that controls the cell cycle and functions as a tumor suppression. a. p21 b. p53 c. Cdk d. Cdc 2. Mutations are alterations to a a. cell’s nucleus b. chromosome c. DNA sequence d. cell’s cycle 3. These give cancer cells the ability to create new passageways in tissues. a. proteases b. tumors c. proteins d. oncogenes 4. Proto-oncogenes become __________ when mutated. 58 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 a. tumors b. antibodies c. oncogenes d. carcinomas 5. Programmed cell death is called a. apoptosis. b. metastasis c. Cdk.. d. Gap 0. Let’s Analyze Activity 5. In this activity, elaborate your answer to each of the questions below: 1. Why does the body need a normal p53 gene? The body needs a normal p53 gene because it acts as a tumor suppressor, helping to prevent the formation of tumors by regulating the cell cycle. p53 can detect DNA damage and either repair the damage or trigger apoptosis to eliminate damaged cells. Without a functional p53 gene, damaged cells may continue to divide uncontrollably, leading to the development of cancer. 2. Differentiate benign from malignant. Benign tumors are non-cancerous growths that do not spread to other parts of the body and are usually localized. Malignant tumors, on the other hand, are cancerous and have the ability to invade surrounding tissues and spread to other areas through the bloodstream or lymphatic system (metastasis). While benign tumors can often be removed and do not typically pose a serious health threat, malignant tumors can be life-threatening and require more aggressive treatment. 3. How can you reduce the chance of acquiring cancer? To reduce the chance of acquiring cancer, it's important to avoid smoking and limit alcohol consumption, as both are known risk factors for various types of cancer. Maintaining a healthy diet, exercising regularly, and protecting yourself from excessive sun exposure can also help lower the risk. Additionally, regular screenings and early detection can catch cancer at its earliest stages, improving the chances of successful treatment. In a Nutshell Activity 5. Based from the definition of the most essential terms and concepts in the study of cancer cells and the learning exercises that you have done, please feel free to write your arguments or lessons learned below. 1. 59 | P a g e  College of Arts and Sciences Education General Education – Science 2nd Flr. DPT Building, Matina Campus, Davao City Phone No. : (082)300-5456/305-0647 Local 134 2. 3. Q&A List Do you have any question for clarification? Questions/Issues Answers 1. 2. 3. 4. 5. Keywords Index cancer apoptosis metastasis mutation mutagen carcinogen benign malignant 60 | P a g e