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Cancer

Cancer. Lecture 42 BSCI 420,421,620 Dec 11, 2002 “Cancer cells break most of the basic rules of behavior by which multicellular organisms are built and maintained.” - Bruce Alberts Cancer as a microevolutionary process Principles of Oncogenesis Oncogenes (lecture 43).

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Cancer

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  1. Cancer • Lecture 42 BSCI 420,421,620 Dec 11, 2002 • “Cancer cells break most of the basic rules of behavior • by which multicellular organisms are built and maintained.” • - Bruce Alberts • Cancer as a microevolutionary process • Principles of Oncogenesis • Oncogenes (lecture 43)

  2. Cancer as a microevolutionary process • Because our bodies are complex societies of billions of cells, • some rules are necessary for the good of the entire organism. • “Cancer cells break most of the basic rules of behavior • by which multicellular organisms are built and maintained.” • What are those rules? • You shall behave like the other cells of your type, • e.g. only divide when told to do so by a mitogenic factor. • You shall maintain contacts or junctions with your neighbors • if you are in an epithelium. • You shall not go wandering off into other parts of the body • without permission. • If you are virus infected or your DNA is severely damaged, • you shall undergo apoptosis for the good of the whole.

  3. Cancer is a disease (or group of diseases) in which individual • mutant clones of cells proliferate, spread, and can destroy the • entire organism. • Some terminology: • A tumor is an abnormally growing clone of cells. • A tumor is benign if it remains together as a single mass • (surgury or local irradiation highly successful). • A tumor is malignant (or a cancer) if it invades other tissues. • Cancers of epithelial cell are called carcinomas. • Cancers of connective tissue or muscles are sarcomas. • Cancers of the blood cells are called leukemias.

  4. Principles of Oncogenesis (Formation of a cancer): • Cancers arise from a single cell. • Cancers are initiated by somatic mutation. • Carcinogens cause mutations in DNA • a. Chemical – many synthetic or natural chemicals • b. Physical – UV radiation -> skin cancer • c. Biological – tumor viruses • 4. Carcinogens can cause mutations in different ways. • a. Point mutations (eg. That activates an oncogene) • b. Deletions (e.g. of a tumor suppressor gene) • c. Gene amplification (to increase expression of an oncogene) • d. Virus insertion • e. DNA rearrangement or translocation (fig 23-5)

  5. 3 ways a proto-oncogene can be made overactive to convert It to an oncogene:

  6. Two ways of amplifying an oncogene (myc) • Multiple minute chromosomes containing the myc gene. • Multiple copies of myc on the same chromosome • Myc yellow fluor • cDNA hybridized • in situ • DNA - red

  7. Translocation between human chromosomes 9 & 22 puts the myc gene next to an active promoter of an Immunoglobulin gene in a pre-B lymphocyte and induces a leukemia. Creates a “Philadelphia” chromosome.

  8. A mutation may inactivate a tumor suppressor gene, • e.g. p53 or pRB. An inherited heterozygous mutant RB gene • may predispose a person to developing cancer, even at an early • age (Retinoblastoma in children)

  9. Six ways of losing the remaining RB gene

  10. Oncogenesis is a multi-step process: eg. Colon cancer

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