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25 Cards in this Set
- Front
- Back
- 3rd side (hint)
Examples of Oncogenes
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EGF-R2 (Her2), Ras, Raf, Src, Myc
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examples of tumor suppressor genes
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RB, p53, PTEN
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Most of the mutations in cancers are:
a)passenger mutations b)driving mutations |
a)passenger mutations
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Total number of discover tumor suppressor and oncogenes?
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70 TSGs
47 oncogenes |
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outline the mechanism of RB promotion of cancer
cyclin mutations and p53 and their associated cancers |
RB gene deletion
or inactivation by phosphorylation: inc cyclins (D & E) or less CDK inhibitors (p21(due to mutant p53), p16, p27) are made --> activated CDK --> phosphorylation of RB --> releases transcription factors --> cell cycle progresses |
E- breast, colon, stomach, endometrium
D- breast, colon, pancrease p53- breast, colon, panrease |
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normal mechanism of activation and inactivation of Ras
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activation by GEFs (GTP binding)
inactivation by GAPs (GTPase activating proteins) |
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5 effectors of K-Ras induced Benign Pancreatic Tumors (PanINs)
side 3: what these effects are |
-Rho/Rac
-Raf/Mek/Erk/cyclin D1 -Akt -proteases -VEGF |
-abnormal cell morphology (polarity loss)
-proliferation -cell survival & blocking apoptosis -tumore cell invasion -tumor angiogenesis |
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normal B-Raf vs 2 mutant B-rafs
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B-raf: recruited to membrane by Ras, activates its kinase domain through dimerization
mutant B-Rafs: constituitively signal to MEK w/o Ras, one form is truncated and thus not inhibited by vemurafenib |
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two ways of monitoring B-Raf activity
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1)immunostaining for phosphorylated ERK and proliferation by Ki67 (a polymerase only in growing cells)
2) fluorodeoxy-glucose (FDG) uptake in cells with B-Raf induced inc metabolic activity |
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Which one of the following are pro-apoptotic vs anti-apoptotic?
-Bcl-2 -Bad -Bax -Bcl-XL |
Anti-apoptotic: Bcl-2, Bcl-XL
Pro-apoptotic: Bad, Bax |
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constitutive activation of EGF-R results in what?
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activation of:
Akt (prosurvival and anti-apoptotic) pathway Erk (MAPK) pathway STAT pathways |
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Akt is commonly constitutively active in which cancer?
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lung cancer
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actions of PTEN?
mutated PTEN often found in? |
inhibitor of Akt ptw (turns PIP3 back into PIP2)
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prostate cancers
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IGF mechanism of action
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Activates both the growth stimulation Ras/Raf/MEK/MAPK/Cyclin D pathway and the anti-apoptotic PI3K/PIP3/Akt pathway
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EGFR and breast cancer
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HER2(erb2) is truncated, thus constitutively active, phosphorylates HER3 (erb3) which activates the Akt pathway
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definition and actions of ATM?
pt's with mutant ATM are prone to? |
protein kinase that senses DNA damage and phosphorylates p53
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lymphomas as a result f ionizing radiation
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different actions of p53 depending on the amount of cell damage
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low damage: phosphorylated at serine 15 & 20 --> transciption of p21 --> halt cell cycle
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high damage: phosphorylated at serine 15, 20, & 46 --> transciption of Bax --> release of cytochrome C --> activation of caspases --> apoptosis
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mechanism of Bcl-2
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anti-apoptosis by tethering cytochrome C to mitochondrial membrane
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two examples of non-receptor tyrosine kinases activated by chromosomal translocation
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Bcr-Abl fusion protein (9/22)
--seen in which cancer? C-Myc(translocation of IG locus of chrom 15) --seen in which cancer? |
CML
Burkitt Lymphoma |
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mechanism of unlimited lifespan of tumors
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upregulated expression of telomerase, a reverse transcriptase and RNA component, late in Tumor progression which stabilizes aneuploid chromosomes
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mechanism of SV40 infection
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T antigen expressed by the virus binds and inactivates pRB and p53
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Mechanism by whcih mutant Ras and p53 enhance tumor angiogenesis
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ras induces expression of VEGF-- what else can induce this expression in tumors?
p53 induces thrombospondin gene (potent inhibitor of angiogenesis) |
tumore hypoxia induces HIF-1 alpha, a transcription factor for VEGF
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mechanism of invasion of ECM in tumor metastasis
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1- decreased E-cadherin expression (loosens cells)
2-basement membrane degradation by proteases -autocrine mobility factors |
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K-Ras mutant + deletion of CDK inhibitor p16 leads to...
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localized carcinoma
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K-ras mutation + mutant p53 leads to...
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carcinoma with metastasis
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