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Molecular Biology of Cancer

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?

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Molecular Biology of Cancer

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  1. 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.”

  2. 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”

  3. 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.

  4. 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**

  5. Proto-oncogenes into Oncogenes

  6. Alterations of Chromosome Structure

  7. Oncogenes • http://www.teachersdomain.org/asset/tdc02_vid_oncogene/

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

  9. 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

  10. 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.

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

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

  13. 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?

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

  15. 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)

  16. Khan • http://www.youtube.com/watch?v=RZhL7LDPk8w

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

  18. Answer: • True

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

  20. Answer: • False

  21. Question: • What is translocation?

  22. Answer: • Exchange of information from one chromosome to another.

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

  24. 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.

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

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

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

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

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

  30. 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.

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

  32. Answer: • True

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

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

  35. Question: • BRCA genes are ___________________ genes.

  36. Answer: • Tumor-suppressor

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