Neoplasia 2 Flashcards
expression mutated gene, abnormal expression quiescent gene, gene amplification, loss growth inhibitory genes
expression mutated gene, abnormal expression, quiescent gene, gene amplification, loss growth inhibitory genes
nuclear regulatory proteins
myc, myb, jun, fox
nuclear regulatory protein in Burkitt’s lymphoma
c-myc
nuclear regulatory protein in neuroblastoma
N-myc
tumor supressor genes -> must have loss of BOTH copies
RB, p53, NF-1, DCC (deleted in colon cancer)
cancers with high correlation of ras mutation
colon, pancreas, thyroid (glandular)
single most common abnormality of dominant oncogenes in human tumors
ras
two hit hypothesis of retinoblastoma (40% familial cases, malignant retinal tumor)
one mutated from parent, other does somatic mutation
single most common target for genetic alterations in human cancer (RECESSIVE also)
p53
this oncogene acts as “policeman” to inhibit division of genetically damaged cells to allow for repair (quiescence, senescence, or apoptosis) -> typically UV light damage and carcinogenesis
p53
p53 can cause this: temporal cell cycle arrest that allows for repair
quiescence
p53 can cause this: induction of permanent cell cycle arrest (if repair doesn’t happen)
senescence
what mediates cell cycle arrest in p53 action?
CDK inhibitor p21
what mediates apoptosis from p53 activation?
BAX
these tumors are more susceptible to chemotherapy and radiation
normal p53
what is a complete carcinogen?
carcinogen that induces initiation and promotion
what can carcinogens (reactive electrophiles) attack?
DNA, RNA, proteins
chemical carcinogen associated with angiosarcoma of the liver
vinyl chloride (PVC)
fungus that infects peanuts -> has aflatoxin B1
aspergillus flavus
Aspergillus flavus is associated with this cancer
hepatocellular carcinoma
malignant forms of HPV have these proteins that cause cancer; what do they inactivate?
E6 and E7; p53, Rb (respectively)
ways you can look for clonality (expression of specific alleles in daughter cells)
methylation patterns, indicators identical gene RAR (like Ig and T cell isotype)
primary target for genetic damage in neoplasm formation
growth regulatory elements
4 classes of normal regulatory proteins that are targets for alteration causing autonomous proliferation
growth promoting oncogenes, growth inhibiting tumor suppressor genes, genes regulating apoptosis, genes regulating DNA repair
non-altered gene present in normal cells that can then become altered or expressed
proto-oncogene
oncogenes that promote growth are these kind -> only need one allele mutated; what are some examples?
dominant; RAS, GF, GFR
oncogenes that inhibit growth are these kind -> BOTH alleles must be mutated; what are some examples?
recessive; p53, Rb
what is necessary for total unregulated growth to occur in oncogenesis?
constitutive expression multiple positive growth signals and loss inhibitory signals
when does the first restriction point occur in cell cycle?
after G1
regulates orderly progression through the cell cycle phases
cyclins and CDKs
these phosphorylate critical regulatory proteins in the cell cycle
CDKs
this activates CDK, which then activates Rb; what phase is it present in?
cyclin D; mid G1 (disappears in S due to ubiquitin-proteasome)
EF2 transcription
E2F transcription
this cyclin/CDK permits DNA replication (through the S phase)
cyclin E/CDK2
this regulates mitotic prophase
cyclin A/CDK2
this regulates nuclear division
cyclin B/CDK1