MCM Final - Cancer and Aging Flashcards
neoplasm
tumor (abnormal mass or growth)
neoplasia
new growth
tumor progression
natural selection and genomic instability occur
cancer cells
more heterochromatin
-silenced gene that would normally block division
viruses and cancer
15% of human cancer thought to arise from viruses
usually DNA virus
proto-oncogene
gain of function can drive a cell toward cancer
-only requires one allele mutation (dominant-like)
“overactivity mutation”
tumor supressor gene
act in a recessive manner (loss of function)
need mutations in both alleles (recessive like)
“underactivity mutation”
DNA maintenence genes
mutations result in genomic instability
two hit hypothesis
involved in the tumor supressor gene
may be a mix of epigenetic and genetic changes
what DNA damage from cigarettes?
intercalating agent that results in the bulky lesion
-conjugated ring structure
nucleotide excision repair- repairs bulky lesions
benzo [a] pyrine
molecule in tobacco smoke that is a mutagen
- created by cytochrome p450 - converted into benzo[a]pyrene 7,8-diol
causes intercalation of DNA
-bulky lesion
DNA damage from sun exposure?
pyrimidine dimers
-bulky lesions
repaired by nucleotide excision repairs
damage from UVA and UVB
UVA oxidative stress
UVB - dimer formation between pyrimidines
SNPs
involved in nucleotide excision repairs
-different expression can lead to different rates of this mechanisms in individuals
Ras
protooncogene
point mutation affects the hydrolysis of GTP from Ras
constitutively active Ras protein results in mitogenic activation
Myc
transcription factor
constitutively expressed
mutations result in cell division with DNA damage
which cancer protein acts in a dominant manner?
oncogenes
Bcl2
involved in the intrinsic pathway of apoptosis
cytochrome c from mito
Bcl2 family acts on cytochrome c release
proapoptotic proteins - oncogen or TS?
tumor supressor
anti-apoptotic proteins - oncogene or TS?
oncogene
Rb
retinoblastoma
-most common in childhood
supresses activation of S-phase genes
allows cell cycle to continue
Li-Fraumeni syndrome
heritable mutation in p53
only one somatic mutation can lead to p53 inactivity
-already have one mutation
DNA damage checkpoints
G1 to S, Slow S, and S to M
ATM protein activated when DNA damage present
-initiates the p53 > p21 cascade
APC
mutation in this gene leads to familial adenomatous polyposis
autosomal dominant with 100% penetrance
involved in the Wnt pathway (frizzled receptor)
tumor supressor
classical adenoma-carcinoma sequence
adenoma - benign
carcinoma - malignant
what are the proto-oncogenes and tumor supressors?
proto-oncogenes - Ras Bcl2 Myc
Tumor Supressors - Rb p53 APC
Von Hippel Lindau Syndrome
VHL is a tumor suppressor
angiogenic switch
induced by hypoxia
Hif1 marked for degradation by VHL (normoxia)
loss of function of VHL - always on Hif1 - lots of angiogenesis
warburg effect
hypoxic environment in solid tumor
anaerobic glycolysis to get ATP
vessels in tumors?
heterogenous diameter
tortuous - not regular in shape
leaky
neuronal cells have high metabolic activity
increase in oxidative damage
