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23 Cards in this Set
- Front
- Back
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What type of cancer will result from cells originating in (a) epithelial (b) mesenchymal (c) WBCs
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(a) carcinoma (b) sarcoma (c) leukemia/lymphoma
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What are the differences btw familial vs. sporadic cancer?
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Familial -- Involves germline and somatic mutations; multiple tumors, early onset, bilateral. Sporadic -- Two somatic mutations; 1 tumor, later onset, unilateral.
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What is the mechanism by which cigarette smoke causes DNA mutations?
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Polycyclic hydrocarbons (from smoke) converted to epoxides via aryl hydrocarbon hydroxylases (CYP) leading to mutations. (Note: enzyme is inducible and in pts w/hi-inducability allele will be more prone to CA)
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What class of proto-oncogenes and what CA is caused by the following oncogenes (a) Abl (b) Myc (c) Bcl2
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(a) tyrosine kinase, CML (b) transcription factor, Burkitt lymphoma (c) Antiapoptotic factors, CML/follicular lymphoma
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What translocation has been assoc. with Burkitt lymphoma?
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MYC proto-oncogene from chromosome 8 to 14 resulting in expression by promoter region of IG heavy chain genes.
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What chromosomal translocation is associated with CML?
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ABL proto-oncogene translocates from 9 to 22 and is joined by BCR resulting in inc. tyrosine kinase activity creating excess myeloid precursors.
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Describe the mechanism of the following viruses in CA (a) HPV (b) HTLV-1
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(a) Viral proteins inactivate tumor suppressors Rb and p53 (b) Tax protein of virus is a coactivator for proto-oncogenes resulting in T cell leukemia
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Describe the mechanism of the following viruses in CA : HIV
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Tat transcription factor of the virus activates synthesis of cytokines promoting T cell proliferation and causing non-Hodgkin lymphoma
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Describe the 3 main proteins involved in the regulation of the cell cycle.
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Cyclins (inducible) must combine to cycline dependent kinases (constitutive) to become active. There are also cyclin dependent kinase inhibitors (inducible).
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How do activated cyclin dependent kinases act on the cell?
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Phosphorylate retinoblastoma protein causing it to dissoc. from E2F transcription factor. Thus, E2F can cause cell cycle progression from G1 to S. Mutation of Rb leads to retinoblastoma.
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What is p53?
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It is a tumor suppresing transcription factor. p53 initiates transcription of repair enzymes and p21 (a CKI) leading to cell cycle arrest.
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What is the inheritance pattern and cause of Li-Fraumeni syndrome?
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Autosomal dominant. Caused by p53 mutations leading to many different cancers.
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What is neurofibromin (NF-1)?
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Deactivates RAS by hydrolyzing GTP. (RAS is active in MAP kinase cascade).
Mutation in NF-1 can lead to neurofibromatosis. |
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What are cadherins and catenins? Specifically what is beta catenin?
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Cadherins - mediators in cell to cell contact (tumor suppressor). Catenins - bind actin to cadherins. B catenin is also a transcription activator (proto-oncogene).
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How is beta catenin usually regulated? What CA is assoc. with this regulation pathway?
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Inactive by being bound to cadherins and APC (adenomatous polyposis coli). APC mutatations lead to familial polyposis colon CA.
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What pathologies are assoc. with RecQ BLM helicases?
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Bloom's syndrome. Werner syndrome (premature aging). Rothmund-Thompson syndrome (skin abnormalities).
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What are caspases?
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Cysteine proteases secreted as proenzymes and activated by proteolytic cleavage to induce apoptosis.
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What number caspases are initiators? Execution?
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8,9,10.
3,6,7. |
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What cascade occurs after mitochondria perceives death signals?
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Release of CYM C from mitochondria. Binds to apoptotic protease activating factor 1 (Apaf1) and activates capase 9.
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Name 3 anti-apoptotic proteins and describe their function.
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BCL-2, BCL-X, BCL-W. Can bind and inactivate Apaf 1 and antagonize the actions of proapoptotic factors.
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Name 3 pro-apoptotic channel forming proteins and describe their function.
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BAX, BAK, BOK. Form channels in mitochondrial membrane -- releasing CYM C. Dependent on binding of BH3 only members.
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Name 3 pro-apoptotic BH-3 only proteins and describe their function.
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BAD, BID, BIM. Regulate anti and pro-apoptotic factors.
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What translocation is involved in follicular B cell lymphoma?
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BCL-2 translocation from 18 to 14 and places it under promoter control of IG heavy chain genes. Elevated BCL-2 proteins lead to dex. cell death and lymphoma.
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