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RQ10 - Name Key Due Review Questions Oncogenes 1 Give 3...

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Unformatted text preview: Name: Key , Due: Review Questions - Oncogenes 1. Give 3 types of evidence that cancer occurs through a multistep process. a. Typically, cancer incidence increases sharply with age. E.g., cancer o: (age)n, where n represents the number of rate~limiting steps. b. Tumors develop from lesions that are oniy mildly abnormal through increasingly severe stages, eventually resulting in malignant growths capable of metastasizing. c. Tumors at different stages have DNA exhibiting accumulating damage at the later (more malignant) stages. The damage seems to occur in a sequence of chromosomal abnormalities and oncogene activation. 2. Cancer seems to be an imbalance between positive and negative growth stimuli. Describe how oncogenes and tumor suppressor genes fit this scenario. (You may illustrate with specific hypothetical pathways.) Generally oncogenes are derived from protc-oncogenes, whose normal function involves growth stimulation. These genes ordinarily participate in signalling pathways by turning on and off in response to signals they receive. However, if they are derived from damaged genes so they are always turned on and cannot turn off, this produces an imbalance in the signalling pathway, increasing the propensity of the cells to grow. Tumor suppressor genes appear to produce proteins that normally function in growth inhibition. if they are damaged so this function cannot be carried out, an imbalance will result which tilts toward excessive growth. 3. Describe how genetic damage can lead to alteration in proto-oncogene expression (a) or biochemical properties (b) leading to neoplasia. a. Chromosome breakage and rejoining can transfer a proto~oncogene to a new chromosomal location where it is expressed at high levels (not subject to its normal regulation of expression). Burkitt's lymphoma in humans provides an example. b. Point mutations can produce an oncogene whose protein product is no ionger subject to its normal regulation. A ras protein which does not turn oil can occur in this way in humans (or animals). Sister chromatid exchange can produce a damaged proto-oncogene which lacks a regulatory region on the protein. The Phiiadelphia chromosome in humans codes for a damaged kinase (bcr/abl) that is constitutivety active. ...
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