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Questions and Answers
Which characteristic is NOT commonly associated with malignant tumors?
Which characteristic is NOT commonly associated with malignant tumors?
What process is described as a multi-step transformation of normal cells into cancerous cells?
What process is described as a multi-step transformation of normal cells into cancerous cells?
What method can be used to assess altered energy metabolism in tumors?
What method can be used to assess altered energy metabolism in tumors?
Which of the following is indicative of loss of anchorage dependence in tumor cells?
Which of the following is indicative of loss of anchorage dependence in tumor cells?
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What technique is used to evaluate the invasion potential of cancer cells?
What technique is used to evaluate the invasion potential of cancer cells?
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What role do acetyltransferases primarily play in relation to pro-carcinogens?
What role do acetyltransferases primarily play in relation to pro-carcinogens?
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What type of agent results from the oxidation of carbon atoms, creating a carbonim ion or aliphatic epoxide?
What type of agent results from the oxidation of carbon atoms, creating a carbonim ion or aliphatic epoxide?
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Which factor does NOT influence the formation of DNA adducts by electrophiles?
Which factor does NOT influence the formation of DNA adducts by electrophiles?
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What characteristic of the Ames Test is crucial for identifying mutagens?
What characteristic of the Ames Test is crucial for identifying mutagens?
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What is a notable challenge in identifying cancer susceptibility from environmental exposures?
What is a notable challenge in identifying cancer susceptibility from environmental exposures?
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What is the primary role of oncogenes?
What is the primary role of oncogenes?
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Which of the following best describes a proto-oncogene?
Which of the following best describes a proto-oncogene?
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What genetic alteration is indicative of the Philadelphia chromosome?
What genetic alteration is indicative of the Philadelphia chromosome?
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How does gene amplification contribute to cancer?
How does gene amplification contribute to cancer?
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What is a characteristic of tumor suppressor genes (TSGs)?
What is a characteristic of tumor suppressor genes (TSGs)?
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What evidence suggests multiple oncogene activation in certain types of cancer?
What evidence suggests multiple oncogene activation in certain types of cancer?
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What is a common model used to discover tumor suppressor genes?
What is a common model used to discover tumor suppressor genes?
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Which of the following alterations is NOT typically associated with cancer development?
Which of the following alterations is NOT typically associated with cancer development?
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What is the result of a mutation in pRb?
What is the result of a mutation in pRb?
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Which protein is primarily responsible for slowing the G1 to S phase transition?
Which protein is primarily responsible for slowing the G1 to S phase transition?
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What is the effect of a damaged p53 protein on cancer cell behavior?
What is the effect of a damaged p53 protein on cancer cell behavior?
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What role does NF1 play in cellular signaling?
What role does NF1 play in cellular signaling?
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How does the E6 protein of HPV contribute to cancer progression?
How does the E6 protein of HPV contribute to cancer progression?
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What mechanism does HBV utilize for viral protein synthesis after infection?
What mechanism does HBV utilize for viral protein synthesis after infection?
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Which of the following is a mechanism by which RNA viruses can promote cancer?
Which of the following is a mechanism by which RNA viruses can promote cancer?
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What is the consequence of the absence of functional p21 due to p53 mutation?
What is the consequence of the absence of functional p21 due to p53 mutation?
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What role does reverse transcriptase play in the life cycle of the virus?
What role does reverse transcriptase play in the life cycle of the virus?
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Which cyclins are primarily involved in the transition from G1 to S phase of the cell cycle?
Which cyclins are primarily involved in the transition from G1 to S phase of the cell cycle?
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What is indicated by the overexpression of cdc25A/B in breast cancer prognosis?
What is indicated by the overexpression of cdc25A/B in breast cancer prognosis?
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What is the main function of Bcl-2 in the context of apoptosis?
What is the main function of Bcl-2 in the context of apoptosis?
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Which of the following is a characteristic of the KIP family of CDK inhibitors?
Which of the following is a characteristic of the KIP family of CDK inhibitors?
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How does the loss of expression of Apaf-1 contribute to tumor development?
How does the loss of expression of Apaf-1 contribute to tumor development?
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Which method is NOT a typical indication of apoptosis detection?
Which method is NOT a typical indication of apoptosis detection?
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What happens during the assembly of new virus particles?
What happens during the assembly of new virus particles?
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Which of the following statements about oncogenic potential is correct?
Which of the following statements about oncogenic potential is correct?
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What is the primary disadvantage of the dextran-coated charcoal method?
What is the primary disadvantage of the dextran-coated charcoal method?
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Study Notes
Hallmarks of Cancer
- High mitotic index: refers to a high rate of cell division.
- Morphological changes: including disorganized cytoskeleton and abnormal cellular appearance.
- Loss of cell contact inhibition: cells continue to proliferate even when they are in contact with each other.
- Loss of growth regulation: cells continue to grow even when they are not receiving growth signals.
- Loss of dependence on anchorage for growth (anchorage-independent growth): cells can grow in suspension, without being attached to a solid surface.
- Altered gene expression: changes in gene expression can result in the production of proteins that promote tumor growth and spread.
- Malignant tumors: can invade surrounding tissues and spread to other parts of the body (metastasize).
- Benign tumors: do not invade surrounding tissues or metastasize.
- Invasion: the process by which tumor cells invade surrounding tissues.
- Altered energy metabolism (Warburg effect): cancerous cells rely heavily on glycolysis for energy production, even in the presence of oxygen.
Methods to Study Cancer
- Eosin staining: used to stain the cytoskeleton, particularly useful in the study of breast cancer.
- Scanning electron microscopy: used to observe the accumulation of cells due to loss of cell contact inhibition.
- Growth factors within a petri dish: used to study the loss of growth regulation in cancer cells.
- Spherical colonies with attachment to solid substrate: used to study anchorage-independent growth in cancer cells.
- Gene expression arrays: used to study changes in gene expression in cancer cells.
- Injection of cells into mice: used to test the malignant potential of cells.
- Matrigel invasion assay: used to study the invasiveness of cancer cells.
- PET scans: used to detect if tumor cells have accumulated radioactive glucose, which is a hallmark of the Warburg effect.
Cancer as a Multi-step Process
- Cancer development is a multi-step process that involves multiple genetic alterations in normal cells, transforming them into cancerous cells.
Causes of Cancer: Electrophilic Molecules
- Different types of cancer are caused by different agents, which often involves the action of electrophilic molecules.
Types of Electrophilic Molecules
- Alkylating agents: alkylate DNA by adding alkyl groups, often through oxidation of carbon atoms to form carbonium ions or aliphatic epoxides.
- Aryl(aromatic) aminating agents: form aromatic amines or amides, often through oxidation or reduction of nitrogen atoms, producing aryl nitrenium ions (with a positive charge on nitrogen).
- Aralkylating agents: generally polycyclic aromatic hydrocarbons, often forming aromatic epoxides.
DNA Adducts
- Electrophilic molecules can react chemically with DNA bases, forming DNA adducts. This depends on the electrophile's ionic nature and the specific atom it reacts with.
Challenges in Cancer Research
- Long latent period: there can be a significant delay between exposure to a carcinogen and the clinical detection of a tumor.
- Difficult to quantify exposure: it is often challenging to determine the type and amount of exposure to carcinogens.
- Multiple exposures: Individuals are often exposed to multiple chemicals and other cancer-causing agents, making it difficult to pinpoint specific causes.
- Genetic variability: individuals differ in their susceptibility to cancer due to variations in their genes.
- Low exposure levels: it can be difficult to detect exposure to carcinogens at low doses, as these may still have carcinogenic effects.
Assays to Study Carcinogenicity
- Transformed fibroblast assay: used to study the ability of a substance to transform normal cells into cancer cells.
- Ames test: used to test for mutagenicity. Many chemicals identified as carcinogens in animal experiments and cell cultures are also mutagenic.
- Mutagenicity vs. carcinogenicity: While mutagenicity is often associated with carcinogenicity, not all mutagens are necessarily carcinogenic, because DNA repair mechanisms and metabolism can play a role in protecting cells from damage.
- Mechanism of the Ames test: uses mutant Salmonella bacteria that cannot synthesize histidine (HIS). These bacteria cannot grow in a medium lacking histidine. Mutagens can cause a reversion of the mutation back to HIS independence, allowing the bacteria to grow in the medium. The number of revertant colonies is a measure of the mutagenic potency.
Oncogenes and Tumor Suppressor Genes
- Oncogenes: any gene that encodes proteins that can cause transformation of cells in culture, leading to cancer development in animals.
- Proto-oncogenes: the normal, non-mutated versions of oncogenes, often involved in cell growth and proliferation regulation.
- Tumor suppressor genes (TSG): genes that normally inhibit cell transformation in culture or suppress tumor growth in animals.
Mechanisms of Oncogene Activation
- Gene deletion/mutation: loss of function of the gene.
- Gene amplification: increased copy number of the gene, leading to overexpression.
- Chromosomal translocation: rearrangement of genetic material, often resulting in the fusion of two genes and the production of a chimeric protein with oncogenic properties.
Examples of Activated Oncogenes
- p21 ras gene: single point mutation in the 12th codon can activate this gene.
- myc gene: involved in growth and differentiation, its over-expression (due to mutation, amplification, or translocation) leads to tumorigenesis.
- Philadelphia chromosome: a chromosomal translocation involving the c-abl gene from chromosome 9 to chromosome 22, often found in chronic myeloid leukemia.
Tumor Suppressor Genes
- pRb: a key regulator of the cell cycle, controlling the transition from the G1 phase to the S phase.
- p53: a critical tumor suppressor gene that plays a central role in DNA damage repair, cell cycle arrest, and apoptosis.
- NF1: normally converts RAS into its inactive form, inhibiting RAS signaling. Loss of NF1 function leads to continuous activation of RAS and uncontrolled cell growth.
Viruses and Cancer
- Many viruses have been implicated in cancer development. These viruses can:
- Carry oncogenes: the viral genome can contain genes that promote uncontrolled cell growth.
- Insertional mutagenesis: integration of the viral genome into the host DNA can disrupt the function of tumor suppressor genes or activate oncogenes.
- Activate host genes: the virus can stimulate the expression of host genes that promote cell growth.
Examples of Cancer-Causing Viruses
- Epstein-Barr virus (EBV): associated with Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma.
- Human papillomavirus (HPV): associated with cervical cancer, head and neck cancers, and anal cancer.
- Human T-lymphotropic virus (HTLV- 1 and 2): associated with adult T-cell leukemia and lymphoma.
- Hepatitis B and C viruses (HBV and HCV): associated with liver cancer.
- Kaposi's sarcoma-associated herpesvirus (KSHV): associated with Kaposi's sarcoma.
- Merkel cell polyomavirus (MCV): associated with Merkel cell carcinoma.
Mechanisms of Viral Carcinogenesis
-
HPV:
- E5 protein: interacts with growth factor receptors, activating the MAPK pathway.
-
E7 protein: binds to and degrades
pRb, removing the cell cycle checkpoint. -
E6 protein: binds to and ubiquitylates
p53, targeting it for degradation.
-
HBV:
-
HBx protein: can sequester p53, upregulate genes important for growth, and disrupt the function of the cyclin A and
α-RAR genes.
-
HBx protein: can sequester p53, upregulate genes important for growth, and disrupt the function of the cyclin A and
RNA Viruses and Cancer
- RNA viruses: can also cause cancer, often by integrating their viral genome into the host DNA.
Examples of RNA Virus Pathways
-
HCV:
-
Core proteins: can activate the JNK signal transduction pathway, upregulate NF-κB activity, and inactivate
p53.
-
Core proteins: can activate the JNK signal transduction pathway, upregulate NF-κB activity, and inactivate
Receptor Status in Cancer:
- Different methods to study receptor status:
- Dextran-coated charcoal method: disadvantage is that it requires large amounts of material.
- Immunocytochemical method: an advantage as it is accurate in detecting receptors.
- Immunohistochemistry method: an advantage as it offers direct correlation of histological features with receptor status.
- **Quantitative PCR (qPCR): ** an advantage as it can be used with small amounts of material.
- Receptor status and treatment: it can be used to predict the effectiveness of targeted therapies, such as hormone therapy for breast cancer.
Cancer Cell Proliferation: Cyclins and Cyclin-Dependent Kinnases (CDKs)
- Cyclins: proteins that regulate the cell cycle, with different cyclin proteins expressed during different stages of the cell cycle.
- Cyclin-dependent kinases (CDKs): enzymes that phosphorylate other proteins, controlling the progression of the cell cycle. CDKs are inactive unless bound to a cyclin protein.
- CDK activation: CDKs require the binding of cyclins for activation and phosphorylation by the CDK-activating kinase (CAK).
-
Regulation of CDK activity:
- WEE1: inactivates CDKs by adding a second phosphate group.
- CDC25: activates CDKs by removing the second phosphate group.
Role of Cyclins in Cell Cycle Progression
- D-type cyclins: involved in the G0 to G1 phase transition.
- E-type cyclins: involved in the G1 to S phase transition.
- A-type cyclins: involved in the initiation of S phase.
- B-type cyclins: involved in the G2 to M phase transition.
CDK Inhibitory Proteins (CKIs)
- KIP (kinase inhibitory protein) family: p21, p27, and p57. These proteins bind to and inhibit CDKs 1-6, preventing the cell cycle from progressing.
- INK4 (inhibitory of CDK4) family: specifically inhibits cyclin D-dependent kinases 4 and 6. They destabilize the association between cyclin D and CDK 4/6.
- Myc: a transcription factor that promotes cell proliferation and expression promotes cell cycle entry without growth factors.
Examples of Cell Cycle Regulators in Cancer
- Cyclin E1: gene amplification and translocation are common in cancer cells.
- Cyclin D1: gene amplification and translocation are common in many cancers, including lung cancer.
- Cyclin A: overexpression is often observed in liver and breast cancers.
- CDC25A/B: overexpression is a strong indicator of poor prognosis in breast cancer.
Apoptosis: Programmed Cell Death
- Apoptosis: a process of programmed cell death that is essential for normal development and tissue homeostasis. It is also a key mechanism for eliminating damaged or abnormal cells.
Regulators of Apoptosis
- Stimulators (agonists): molecules that promote apoptosis. Examples include Apaf-1, cytochrome c, and dATP.
- Apaf-1: forms oligomers, which then bind to procaspase 9, processing and activating it. It requires the presence of cytochrome c and dATP.
- Inhibitors (antagonists): molecules that block apoptosis. Examples include Bcl-2.
- Bcl-2: inhibits cytochrome C release, protecting cells from apoptosis.
- Caspases: cysteine proteases that play a central role in executing apoptosis. They are inactive until they are cleaved and activated by specific stimuli.
- Initiator caspases (8, 9, 10): activated early in the apoptotic cascade, they activate executioner caspases.
- Executioner caspases (3, 6, 7): cleave specific substrates, leading to dismantling of the cell.
Methods to Study Apoptosis
- Membrane structure alterations: used to detect changes in membrane structure with fluorescent probes or flow cytometry.
- Cytochrome C release: can study the release of cytochrome C from the mitochondria into the cytosol with immunohistochemistry.
- Caspase processing and substrates: analyzed using Western blots.
- DNA fragmentation: can be observed as DNA laddering or with the TUNEL assay, which detects DNA breaks.
Examples of Apoptosis Regulation in Cancer
- Loss of caspase 8 expression: associated with amplification of the N-myc oncogene.
- Loss of Apaf-1 expression: observed in melanoma cells.
- Overexpression of Bcl-2: observed in various cancers.
Necrosis: Unprogrammed Cell Death
- Necrosis: an unprogrammed form of cell death that occurs in response to severe, uncontrolled damage. It is often characterized by inflammation and the release of cellular contents.
Necrosis and Cancer
- Necrosis can be induced: by drugs that disrupt cellular function.
- Necrosis and anti-tumor immunity: cell death in tumors can initiate an antitumor immune response.
Other important details:
- Treatment: targeted therapies and treatments are increasingly being developed to target the specific molecular alterations that drive cancer.
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Description
This quiz explores the key characteristics that define cancer, including cell division rates, morphological changes, and the behavior of malignant versus benign tumors. Understanding these hallmarks is crucial for comprehensive cancer biology. Test your knowledge on these fundamental concepts related to cancer.
