Molecular Biology of Cancer What are the environmental influences that are cancer-causing? What is the difference between an oncogene and a proto-oncogene? What genetic changes convert proto-oncogenes to oncogenes? Reference page 272 (Fig 15.12) to understand alterations of chromosome structure: relate this to the statement “Malignant cells are frequently found to contain chromosomes that have broken and rejoined incorrectly, translocating fragments.”

Molecular Biology of Cancer (responses) Chemical carcinogens, physical mutagens (X- rays) or certain viruses Proto-oncogene: normal cellular genes-code for proteins that stimulate normal cell growth and division Oncogene: cancer-causing gene “An oncogene arises from a genetic change that leads to an increase in either the amount of proto-oncogene’s protein product or intrinsic activity of each protein molecule”

Cancer Understood Explain how the location of the proto- oncogene being located adjacent to an active promoter leads to an oncogene. What is amplication? Explain how a point mutation can change the gene’s protein product and therefore lead to an oncogene.

Alterations of Chromosome Structure

3 Main Categories of Oncogene Conversion Movement of DNA within the genome – Translocation or transposition – **new controls / new promoter Amplication of proto-oncogene – Increases number of copies of the gene in the cell Point mutation in proto-oncogene – More active or resistance to degradation than normal protein **All growth stimulating**

Proto-oncogenes into Oncogenes

Oncogenes vid_oncogene/ vid_oncogene/

Tumor-suppressors Define and explain tumor-suppressor genes in relationship to cancer. What are the functions of normal tumor- suppressor genes?

Tumor Suppressor Genes Tumor suppressor genes—proteins prevent uncontrolled cell growth Functions: – Repair damaged DNA – Control adhesion of cells to each other – Cell signaling—inhibit cell cycles If altered, the suppression is decreased and therefore cancer can be the outcome

Ras (30%) versus p53 (50%) In general, what is the difference between a oncogene and a tumor suppressor gene? Relate them to cancer. Signal transduction Pathways: A set of chemical reactions in a cell that occurs when a molecule, such as a hormone, attaches to a receptor on cell membrane. The pathway is actually a cascade of biochemical reactions inside the cell that eventually reach the target molecule or reaction. Thus, the pathway is a method by which molecules inside the cell can be altered by molecules on the outside.

Ras Normal ras job: What does ras need to do its job? How is the oncogene of Ras hyperactive?

p53 What are the main functions of a normal functioning p53? (hint: at least 3 ways)

Cancer and Age Why does the incidence of cancer increase with age? How does this help explain the predispositions to cancer that run in some families? Explain “dominant oncogenes and recessive tumor-suppressors”. How do active telomerases relate to cancer?

Viruses How do they contribute to cancer development? Define retrovirus (use back of book)

BRCA1 and BRCA2 What does BRCA stand for? What type of cancers are these genes related to? What type of genes are these? (oncogenes or tumor-suppressors)

Metastasis Tumor Benign Malignant Metastasis

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Question: True or False: A proto-oncogene only makes a protein when a promoter tells it to.

Answer: True

Question: True or False: One possible effect of an oncogene is the inability to repair a damaged cell.

Answer: False

Question: What is translocation?

Answer: Exchange of information from one chromosome to another.

Question: What does translocation have to do with promoters and cancer?

Answer: The “switched gene” goes to a new location with a new promoter that tells it to turn on (make a protein) when it normally would not.

Question: What are the three normal jobs of a tumor- suppressor?

Answer: Repair damaged DNA Control adhesion of cells to each other Cell signaling—inhibit cell cycles

Question: Was the video showing how a mutated Ras works or how a mutated p53 works? Explain.

Answer: Ras. It was stimulating cell growth, not stopping it. Ras is an oncogene, not a tumor- suppressor.

Question: Why is p53 known as the Guardian Angel of the Genome? Why is p53 a part of 50% of all cancers?

Answer: It makes sure all the erred cells do not multiply or continue on with mutations by repairing, signaling to stop cell cycle, or signaling apoptosis. An error in p53 is very detrimental to cells and leads to cell overgrowth…aka cancer.

Question: True or False: A virus can stimulate cancer.

Answer: True

Question: True or False: It only takes a single mutation to cause cancer.

Answer: False. This is why the incidence of cancer increases with age.

Question: BRCA genes are ___________________ genes.

Answer: Tumor-suppressor