Podcast
Questions and Answers
What is the primary characteristic that defines cancer?
What is the primary characteristic that defines cancer?
Cancer is characterized by uncontrolled cell division.
How do oncogenes and tumor-suppressor genes differ in relation to cancer?
How do oncogenes and tumor-suppressor genes differ in relation to cancer?
Oncogenes promote cell division, while tumor-suppressor genes inhibit cell division.
What does it mean for a cancer to be classified as 'metastatic'?
What does it mean for a cancer to be classified as 'metastatic'?
A metastatic cancer has spread to a different site in the body.
Why are most cancers considered clonal in origin?
Why are most cancers considered clonal in origin?
What role do radiation and chemical carcinogens play in the development of cancer?
What role do radiation and chemical carcinogens play in the development of cancer?
What are tumor viruses and their significance in cancer research?
What are tumor viruses and their significance in cancer research?
What is a 'benign growth' in the context of cancer development?
What is a 'benign growth' in the context of cancer development?
Can you name a virus that is associated with causing cervical cancer?
Can you name a virus that is associated with causing cervical cancer?
What is the relationship between Epstein-Barr virus and Burkitt lymphoma?
What is the relationship between Epstein-Barr virus and Burkitt lymphoma?
What percentage of human cancers are not induced by viruses?
What percentage of human cancers are not induced by viruses?
How do oncogenes contribute to cancer development?
How do oncogenes contribute to cancer development?
What is a proto-oncogene?
What is a proto-oncogene?
What role do tumor suppressor genes play in cancer?
What role do tumor suppressor genes play in cancer?
What is the significance of the Rb gene in cancer research?
What is the significance of the Rb gene in cancer research?
How does p53 contribute to cell survival in response to DNA damage?
How does p53 contribute to cell survival in response to DNA damage?
What distinguishes oncogenes from tumor suppressor genes?
What distinguishes oncogenes from tumor suppressor genes?
How does Rb inhibit cell cycle progression?
How does Rb inhibit cell cycle progression?
What role does p16 play in relation to Cdk4,6/cyclin D complexes?
What role does p16 play in relation to Cdk4,6/cyclin D complexes?
What is the significance of wild-type p53 in cellular response to DNA damage?
What is the significance of wild-type p53 in cellular response to DNA damage?
Define the difference between oncogenes and tumor suppressor genes.
Define the difference between oncogenes and tumor suppressor genes.
What occurs when a tumor suppressor gene loses function?
What occurs when a tumor suppressor gene loses function?
List one effect a gain-of-function mutation in a proto-oncogene may have.
List one effect a gain-of-function mutation in a proto-oncogene may have.
In what way are ras genes significant in cancer?
In what way are ras genes significant in cancer?
Identify one type of mutation frequently found in oncogene formation.
Identify one type of mutation frequently found in oncogene formation.
How do the roles of pro-apoptotic Bcl-2 family members influence cancer?
How do the roles of pro-apoptotic Bcl-2 family members influence cancer?
How does the protein p16 influence the cell cycle?
How does the protein p16 influence the cell cycle?
What role does the NF1 protein play in cell division?
What role does the NF1 protein play in cell division?
Describe the function of the APC protein in cell signaling.
Describe the function of the APC protein in cell signaling.
What is the role of p53 as a checkpoint protein?
What is the role of p53 as a checkpoint protein?
How do BRCA1 and BRCA2 proteins contribute to DNA repair?
How do BRCA1 and BRCA2 proteins contribute to DNA repair?
What are the two general categories of tumor-suppressor genes?
What are the two general categories of tumor-suppressor genes?
Explain the concept of epigenetics.
Explain the concept of epigenetics.
How do checkpoint proteins maintain genome integrity?
How do checkpoint proteins maintain genome integrity?
What is a missense mutation and how can it affect tumor-suppressor genes?
What is a missense mutation and how can it affect tumor-suppressor genes?
Define gene amplification and its potential impact on cancer development.
Define gene amplification and its potential impact on cancer development.
Explain the role of chromosomal translocation in cancer development.
Explain the role of chromosomal translocation in cancer development.
What happens to tumor-suppressor genes when their function is lost?
What happens to tumor-suppressor genes when their function is lost?
How does the Rb protein regulate cell division?
How does the Rb protein regulate cell division?
Describe the two-hit model of retinoblastoma.
Describe the two-hit model of retinoblastoma.
What is the main function of the p53 protein in regards to cancer prevention?
What is the main function of the p53 protein in regards to cancer prevention?
Explain the process of apoptosis and its significance in cancer.
Explain the process of apoptosis and its significance in cancer.
What are the two categories of tumor-suppressor genes?
What are the two categories of tumor-suppressor genes?
How does viral integration contribute to cancer development?
How does viral integration contribute to cancer development?
What are DNA methylation and histone modification, and how do they differ from mutations?
What are DNA methylation and histone modification, and how do they differ from mutations?
Describe one way in which epigenetic changes can be associated with human disease.
Describe one way in which epigenetic changes can be associated with human disease.
What is a potential effect of mutations in genes encoding chromatin-modifying proteins?
What is a potential effect of mutations in genes encoding chromatin-modifying proteins?
List two cancers commonly associated with histone acetyltransferase mutations.
List two cancers commonly associated with histone acetyltransferase mutations.
How do environmental agents affect chromatin-modifying proteins?
How do environmental agents affect chromatin-modifying proteins?
What role do polycyclic aromatic hydrocarbons play in cancer development?
What role do polycyclic aromatic hydrocarbons play in cancer development?
Identify one drug being researched for its potential effects on epigenetic changes in cancer.
Identify one drug being researched for its potential effects on epigenetic changes in cancer.
What is the function of the SWI/SNF complex in chromatin remodeling?
What is the function of the SWI/SNF complex in chromatin remodeling?
Explain the significance of histone demethylase in cancer.
Explain the significance of histone demethylase in cancer.
Why may epigenetic changes be considered indirect in some cases?
Why may epigenetic changes be considered indirect in some cases?
What potential outcomes can arise from increased function of chromatin-modifying proteins?
What potential outcomes can arise from increased function of chromatin-modifying proteins?
How can the association between epigenetics and cancer be identified?
How can the association between epigenetics and cancer be identified?
In terms of epigenetics, what are the implications of histone phosphorylation?
In terms of epigenetics, what are the implications of histone phosphorylation?
Discuss how a disease can cause epigenetic changes.
Discuss how a disease can cause epigenetic changes.
Flashcards
Cancer
Cancer
A disease characterized by uncontrolled cell division; a genetic disease at the cellular level.
Cancer Cell Clonal Origin
Cancer Cell Clonal Origin
Cancer originates from a single cell, which divides to form a mass of identical cancer cells.
Multistep Cancer Development
Multistep Cancer Development
Cancer develops in stages, starting with a benign growth that progresses to cancerous growth through genetic changes.
Malignant Cancer
Malignant Cancer
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Metastatic Cancer
Metastatic Cancer
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Oncogenes
Oncogenes
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Tumor Suppressor Genes
Tumor Suppressor Genes
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Cancer-Causing Agents
Cancer-Causing Agents
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Proto-oncogenes
Proto-oncogenes
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Rb gene
Rb gene
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p53 gene
p53 gene
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Cell transformation
Cell transformation
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Mutations (oncogenes)
Mutations (oncogenes)
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Viral oncogenes
Viral oncogenes
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Missense mutation
Missense mutation
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Gene amplification
Gene amplification
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Chromosomal translocation
Chromosomal translocation
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Viral integration
Viral integration
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What is a tumor suppressor gene?
What is a tumor suppressor gene?
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How does the Rb protein inhibit cell division?
How does the Rb protein inhibit cell division?
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What is Apoptosis?
What is Apoptosis?
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Function of p53 protein
Function of p53 protein
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What happens when tumor suppressor genes are inactivated?
What happens when tumor suppressor genes are inactivated?
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How do tumor suppressor genes prevent cancer?
How do tumor suppressor genes prevent cancer?
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Restriction Point (G1)
Restriction Point (G1)
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Rb Protein
Rb Protein
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Cdk4/6-Cyclin D Complex
Cdk4/6-Cyclin D Complex
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p16
p16
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p53
p53
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p21
p21
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PUMA and Noxa
PUMA and Noxa
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Mutation Effects on Proto-Oncogenes
Mutation Effects on Proto-Oncogenes
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Ras Protein
Ras Protein
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E2F Inhibition's Role
E2F Inhibition's Role
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p16's Role
p16's Role
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NF1's Action
NF1's Action
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Loss of NF1 Function
Loss of NF1 Function
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APC's Function
APC's Function
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Genome Integrity
Genome Integrity
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Checkpoint Proteins & DNA Repair
Checkpoint Proteins & DNA Repair
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p53's Role
p53's Role
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Epigenetics
Epigenetics
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Epigenetic Changes and Disease
Epigenetic Changes and Disease
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Epigenetic Changes in Cancer
Epigenetic Changes in Cancer
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Mutations in Chromatin-Modifying Proteins
Mutations in Chromatin-Modifying Proteins
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Epigenetic Changes in Cancer: DNA Methylation
Epigenetic Changes in Cancer: DNA Methylation
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Epigenetic Changes in Cancer: Histone Modification
Epigenetic Changes in Cancer: Histone Modification
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Epigenetic Changes in Cancer: Chromatin Remodeling
Epigenetic Changes in Cancer: Chromatin Remodeling
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Environmental Agents and Epigenetics
Environmental Agents and Epigenetics
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Epigenetic Cancer Treatments
Epigenetic Cancer Treatments
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How do epigenetic changes contribute to cancer?
How do epigenetic changes contribute to cancer?
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What are the main types of epigenetic modifications in cancer?
What are the main types of epigenetic modifications in cancer?
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How do mutations in chromatin-modifying proteins contribute to cancer?
How do mutations in chromatin-modifying proteins contribute to cancer?
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What are some examples of environmental agents that can alter epigenetics?
What are some examples of environmental agents that can alter epigenetics?
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What are the potential therapeutic strategies based on targeting epigenetic changes in cancer?
What are the potential therapeutic strategies based on targeting epigenetic changes in cancer?
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Study Notes
Genetic Basis of Cancer
- Cancer is a disease characterized by uncontrolled cell division.
- It is a genetic disease at the cellular level.
- Human cancers are classified by the type of cell that becomes cancerous.
- More than 100 types of human cancer have been identified.
Characteristics of Cancer
- Most cancers originate from a single cell, and the growth is clonal.
- Cancer cell division produces two cancerous cells.
- Cancer is a multistep process.
- It begins as a non-invasive benign growth.
- Additional genetic changes lead to cancerous growth.
- Cancers can be staged as malignant or metastatic.
- Malignant tumors are invasive, invading surrounding tissue.
- Metastatic tumors move to different sites in the body.
Causes of Cancer
- Radiation and many chemical carcinogens damage DNA and induce mutations.
- Other chemical carcinogens stimulate cell proliferation to contribute to cancer development.
- Viruses, including tumor viruses, cause cancer in both humans and other species.
Tumor Viruses
- Members of several animal virus families, called tumor viruses, cause cancer.
- They are capable of causing cancer in experimental animals and humans.
Tumor Viruses Table
- DNA Genomes:
- Hepatitis B viruses - Liver cancer.
- SV40 and polyomavirus - None
- Papillomaviruses - Cervical carcinoma
- Adenoviruses - None
- Herpesviruses - Burkitt's lymphoma, nasopharyngeal, carcinoma, Kaposi's sarcoma.
- RNA Genomes:
- Hepatitis C virus - Liver cancer
- Retroviruses - Adult T-cell leukemia
Table 22.7 Examples of Viruses That May Cause Cancer
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Retroviruses (RSV) - Cause sarcomas in chickens
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Hardy-Zuckerman-4 feline sarcoma virus - Cause sarcomas in cats
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DNA viruses (Hepatitis B, SV40, polyomavirus) - Cause liver cancer in several species including humans
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Papillomavirus - Causes benign tumors and malignant carcinomas in several species including humans; causes cervical cancer in humans
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Herpesvirus - Causes carcinoma in frogs and T-cell lymphoma in chickens. A human herpesvirus (Epstein-Barr virus) is a causative agent in Burkitt lymphoma, which occurs primarily in immunosuppressed individuals such as AIDS patients.
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The majority (approximately 80%) of human cancers do not appear to be induced by viruses. They result from other causes, such as radiation and chemicals.
Genes, Oncogenes
- Cancer results from alterations in critical regulatory genes that control cell proliferation, differentiation, and survival.
- Specific genes (called oncogenes) induce cell transformation providing insights into cancer's molecular basis.
- Studies of viral oncogenes led to the identification of cellular oncogenes, involved in non-virus-caused cancers.
- Retroviral oncogenes, such as the src gene of Rous sarcoma virus (RSV), were identified in early studies.
Proto-Oncogenes
- Proto-oncogenes are genes normally causing normal cells to become cancerous when mutated.
- Mutations in proto-oncogenes are typically dominant.
- The mutated form of a proto-oncogene is called an oncogene.
- Oncogenes are abnormal or mutated forms of corresponding proto-oncogenes.
Tumor Suppressor Genes
- Tumor suppressor genes function as the opposite side of cell growth control. They normally inhibit cell proliferation and tumor development.
- Tumor suppressor gene Rb was identified, along with p53, in studies of retinoblastoma inheritance.
- Loss or mutational inactivation of Rb and other tumor suppressor genes, contributes to many human cancers.
- The encoded proteins of tumor suppressor genes act as inhibitors of cell proliferation or survival..
Functions of Tumor Suppressor Gene Products
- Rb, INK4, and p53 proteins are negative regulators of the cell cycle progression.
- P53 is required for apoptosis induced by DNA damage or other stimuli, so its inactivation contributes to enhanced tumor cell survival.
Rb Protein Regulates Cell Division
- The Rb protein suppresses the proliferation of cancer cells.
- Rb regulates transcription factor E2F, which activates genes necessary for cell cycle progression.
- Rb binding to E2F inhibits its activity and prevents cell progression through the cell cycle.
- In the absence of functional Rb, a cell can always progress through the cell cycle.
p53
- The p53 gene is a tumor suppressor gene discovered after Rb.
- Approximately 50% of human cancers have defects in the p53 gene.
- The p53 protein is a primary determinant of a cell's response to DNA damage.
- It activates genes that promote DNA repair, arrest cell division, and induce apoptosis.
Apoptosis
- Apoptosis is programmed cell death involving cell shrinkage, chromatin condensation, and DNA degradation.
- It is facilitated by proteases known as caspases.
- In apoptosis, the cell fragments into small vesicles.
- Immune system cells later phagocytose these vesicles.
Epigenetics
- Epigenetics is the study of heritable traits that happen without changes in the DNA sequence, but affect cell function.
- Epigenetic factors can contribute to cancer.
- DNA methylation and histone modification are examples of epigenetics mechanisms that alter gene expression without altering the underlying DNA sequence.
Epigenetic Changes Common in Cancer Cells
- Several chromatin modifications are abnormal in cancer cells, such as DNA methylation, covalent histone modifications, and chromatin remodeling.
Environmental Agents that Alter Chromatin-Modifying Proteins
- Some environmental agents directly alter chromatin-modifying proteins.
- For some agents, an association with cancer is causative.
- Whether other influences are truly causative is not yet known for all agents.
Cancer Treatments Aimed at Epigenetic Changes
- Researchers are investigating drugs to inhibit cancer by affecting DNA methylation or covalent histone modifications.
- 5-azacytidine and decitabine, which are DNA methyltransferase inhibitors, have shown some promise in leukemia treatment.
Mutations Changing Proto-Oncogenes to Oncogenes
- Four common types of mutations change proto-oncogenes to oncogenes: missense mutation, gene amplification, chromosomal translocation, and viral integration.
Oncogenes vs Tumor Suppressor Genes
- Genes involved in cancers are classified as either oncogenes or tumor suppressor genes.
- Oncogenes have a mutated gene that promotes cancerous growth by overexpression.
- Tumor suppressor genes regulate processes that control cancer, stopping or hindering cancer by preventing it. -Loss in function occurs in tumor suppressor genes, causing cancerous growth.
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