Ch 7 Molecular Basis of Cancer Flashcards
8 hallmarks of cancer
self sufficiency in growth signals
insensitivity to growth-inhibitory signals
altered cellular metabolism
evasion of apoptosis
limitless replicative potential (immortality)
sustained angiogenesis
ability to invade and metastasize
ability to evade the host immune response
proto oncogenes
involved in normal cell growth and division
oncogenes
cancer causing genes
change in proto oncogenes that cause them to be more active (mutated or over expressed)
allows the cell the grow and survive when they should not
tumor suppressor genes
involved in fixing damaged DNA
stem cell like properties of cancer cells
lesions that inactivate senescence signals and reactivate telomerase which gives cells limitless replicative potential
oncoprotein
protein encoded by an oncogenes that drives increased cell proliferation through several mechanisms
activation of EGF R TK
point mutation
lung cancer
activation of HER2 TK
gene amplification
breast cancer
activation of JAK2 TK
point mutation
myeloproliferative disorders
activation of ABL non TK
chromosomal translocation
activation of BCL-ABL
fusion gene
CML, ALL
activation of RAS
point mutation
activation of PI3K and BRAF ser/thre kinase
point mutation
MYC
master transcription factor that regulates genes needed for rapid cell growth
induced by RAS/MAPK in quiescent cells by GF
CDK4/D
make a complex that pi RB allowing cells through the G1-S checkpoint
RB
tumor suppressive protein that binds the E2F transcription factors in HYPOpi state stoping G1-S progression
normal growth factor signaling will lead to HYPERpi leading to progression of cell cycle
E7 of HPV binds to and inhibits
p53
tumor suppressor that causes cell cycle arrest and apoptosis through p21
allows for DNA repair
main component of G2-M checkpoint
proteins involved in signal transduction pathway
occurs when a molecule attaches to a R leading to a cascade of biochemical reactions inside the cell that reach the target molecule or site of reaction
two hit of RB
must have 2 defective copies
familial - one inherited and one mutation
sporadic - two mutations
p53 and chemotherapy and radiation
wild (normal) p53- is most effected by these treatments
mutated p53 - resistant
activation of p53
ATM/ATR sense DNA damage and pi p53 removing inhibition by MDM2
APC
adenomatous polyposis coli protein
INHIBITOR OF WNT SIGNALING
F -familial colonic polyps and carcinomas
S - carcinomas of stomach, colon, pancreas, melanoma
NF1
neurofibromin-1
INHIBITOR OF RAS/MAPK SIGNALING
F- nerofibromas and malignant peripheral n sheath tumors)
S - neuroblastoma, juvenile ML
NF2
merlin
CYTOSKELETAL STABILITY, HIPPO PATHWAY SIGNALING
F - acoustic schwannoma and meningioma
S - schwannoma and meningioma
RB syndromes and cancers
retinoblastoma protein
F - retinoblastoma, osteosarcoma, other sarcoma
S - retinoblastoma, osteosacoma, carcinomas of breast, colon, lung
VHL
von hippel lindau protein
INHIBITOR OF HYPOXIA INDUCED TF
F - cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma
S - renal cell carcinoma
CDH1
e-cadherin
CELL ADHESION INHIBITION OF CELL MOTILITY
F - familial gastric cancer
S - gastic carcinoma, lobular breast carcinoma
TP53
p53 protein
CELL CYCLE ARREST & APOPTOSIS IN RESPONSE TO DNA DAMAGE
F - Li-Fraumeni syndrome (diverse cancers)
S - most human cancers
BRCA1 and 2
breast cancer 1 and 2
REPAIR OF DOUBLE STRANDED DNA
F - breast, ovarian, CLL
S - rare
WT1
wilms tumor 1
TRANSCRIPTION FACTOR
F - wilms tumor
S - wilms tumor, leukemias
CML
9;22 ABL BCR
AML
8;21
15;17 - increased risk of bleeding
burkitt lymphoma
8;14
MCY oncogene
mantel cell lymphoma
11;14
follicular lymphoma
14;18
