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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?
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?
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?
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?
1. Thrombospondin
2. Beta-Interferon
3. CD36
What are some mechanisms that lead to Invasion and Metastasis?
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?
1. Cytochrome C
2. APAF
3. Caspace
What intracellular regulators of apoptosis are controlled by ubiquitination and subsequent destruction in the proteosome?
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?
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?
1. Imatinib
2. Gleevec

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