B1 W4 W, Howard 1
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- What is an oncogene?
- gain of function muations
- What is a tumor supressor?
- Loss of function mutation
- An example of Independance from mitogenic stimulation?
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1. A point mutation causes Ras to become constitutively active increasing production of growth proteins
2. Increase in autocrine GF (TGF-alpha and PDGF)
3. Increase in the # of receptors (EGF receptors like Her2 in breast cancer)
*this leads to amplification - An example of Resistance to Growth Inhibition?
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1. Retinoblastoma and the loss of the RB gene
2. TGF-Beta signaling Pathway (bad TGF-B Receptor and loss of CDK inhibition)
3. SMAD mutations prevent the degradation of of cyclins - What controls cellular differentiation?
- Myc and MAD
- What happens when Myc activity is increased?
- Increased: Proliferation and Dedifferentiation
- What happens when Mad is increased?
- The cell is differentiated and terminal i.e normal
- What is an example of uncontrol cell differentiation caused by an increase in Myc activity?
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1. Burkittts Lymphoma (cMyc translocation to Ig promoter)
2. Acute Lymphoblastic Leukemia - What does a mutation in the oncogene RET do?
- constitutively activates the RT-K Receptor
- What type of cancer does a mutation in the oncogene Ras definitely cause?
- Prostate Cancer
- Cancer sensitivity to anti-growth drugs is strongly dependant on what?
- cell cycle
- What is an example of cellular imortality?
- mutations in the Telomerase leads to limitless replication
- What is an angiogenesis inducer?
- VEGF stimulates VEGF Receptors on endothelium
- Whate are some inhibitors of Angiogenesis?
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1. Thrombospondin
2. Beta-Interferon
3. CD36 - What are some mechanisms that lead to Invasion and Metastasis?
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1. Alter Cell to Cell interactions by lowering E-Cadherins and N-CAMs
2. Alter Cell to ECM interaction by changing Integrins
3. Increase Proteases --> destroy ECM and lead to motility - What are some players that SENSE the extracellular enviorment and activation promote Apoptosis?
- TNF Receptors
- What are some pro-cancer players that SENSE the extracellular enviorment and activation inhbit Apoptosis?
- IGF Receptors
- What are some players that SENSE the intracellular enviorment and activation promote Apoptosis?
- p53
- What are some pro-cancer EFFECTORS in the nucleus enviorment upon activation inhbit Apoptosis?
- BCL-2
- What are some EFFECTORS in the nucleus enviorment upon activation promote Apoptosis?
- Bax
- What are effectors from the mitochondria that promote Apoptosis?
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1. Cytochrome C
2. APAF
3. Caspace - What intracellular regulators of apoptosis are controlled by ubiquitination and subsequent destruction in the proteosome?
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1. BCL-2
2. Caspace - How does ubiquitination of I-kB lead to survival?
- normally I-kB inhibits NF-kB (anti-apoptotic protein)
- What are mechanism that lead to Genetic Instability?
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1. mutations in p19 cause p53 to be inhibited by HDM2
2. Mismatch Repair
3. Accumilation of broken and fused chromosomes from bad homologous repair mechanisms - What chemotheraputic drug inhibit the ABL-BCR kinase protein?
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1. Imatinib
2. Gleevec