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25 Cards in this Set

  • Front
  • Back
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Examples of Oncogenes
EGF-R2 (Her2), Ras, Raf, Src, Myc
examples of tumor suppressor genes
RB, p53, PTEN
Most of the mutations in cancers are:

a)passenger mutations
b)driving mutations
a)passenger mutations
Total number of discover tumor suppressor and oncogenes?
70 TSGs
47 oncogenes
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
normal mechanism of activation and inactivation of Ras
activation by GEFs (GTP binding)

inactivation by GAPs (GTPase activating proteins)
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
normal B-Raf vs 2 mutant B-rafs
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
two ways of monitoring B-Raf activity
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
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
constitutive activation of EGF-R results in what?
activation of:
Akt (prosurvival and anti-apoptotic) pathway
Erk (MAPK) pathway
STAT pathways
Akt is commonly constitutively active in which cancer?
lung cancer
actions of PTEN?

mutated PTEN often found in?
inhibitor of Akt ptw (turns PIP3 back into PIP2)
prostate cancers
IGF mechanism of action
Activates both the growth stimulation Ras/Raf/MEK/MAPK/Cyclin D pathway and the anti-apoptotic PI3K/PIP3/Akt pathway
EGFR and breast cancer
HER2(erb2) is truncated, thus constitutively active, phosphorylates HER3 (erb3) which activates the Akt pathway
definition and actions of ATM?

pt's with mutant ATM are prone to?
protein kinase that senses DNA damage and phosphorylates p53
lymphomas as a result f ionizing radiation
different actions of p53 depending on the amount of cell damage
low damage: phosphorylated at serine 15 & 20 --> transciption of p21 --> halt cell cycle
high damage: phosphorylated at serine 15, 20, & 46 --> transciption of Bax --> release of cytochrome C --> activation of caspases --> apoptosis
mechanism of Bcl-2
anti-apoptosis by tethering cytochrome C to mitochondrial membrane
two examples of non-receptor tyrosine kinases activated by chromosomal translocation
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
mechanism of unlimited lifespan of tumors
upregulated expression of telomerase, a reverse transcriptase and RNA component, late in Tumor progression which stabilizes aneuploid chromosomes
mechanism of SV40 infection
T antigen expressed by the virus binds and inactivates pRB and p53
Mechanism by whcih mutant Ras and p53 enhance tumor angiogenesis
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
mechanism of invasion of ECM in tumor metastasis
1- decreased E-cadherin expression (loosens cells)
2-basement membrane degradation by proteases
-autocrine mobility factors
K-Ras mutant + deletion of CDK inhibitor p16 leads to...
localized carcinoma
K-ras mutation + mutant p53 leads to...
carcinoma with metastasis