Biology of Neoplasia II Flashcards
Normal proliferation restricted to the ___ layer orderly differentiation
basal
growth promotion
oncoproteins (oncogenes)
growth inhibition
tumor suppressors
cell free extract injected into chickens caused sarcomas which lead to findings of retrovirus
Rous sarcoma virus
Retrovirus (RSV) contains ____
viral oncogene
Virus detection uses
fibroblast assays
Flat, contact inhibited
non-transformed fibroblasts
If fibroblasts start pilling up
transformed
- single mutation gives growth advantage
- additional mutations increase this
- further mutations activate other cellular properties
Cancer is a result of multiple genetic events
Cells in a tumor should _____ some genetic alterations
share
Combined oncogenes ____ change
increases
Salivary gland metastasis can be caused by ____ loss which is a _____ inhibitor
p16, CDK4
Oncogene activation
1) proliferation
2) survival
3) motility
4) angiogenesis
Mechanisms of oncogene activation
1) point mutation
2) chromosomal translocation
3) gene amplification
Deletion can lead to deregulation making gene always
on
gp55 mimics binding of
erythropoietin (viral oncoprotein)
The ___ pathway is a key target during tumor development
Ras
___ factors can induce transformation
Nuclear
____ is deregulated in Burkitt’s Lymphoma
myc (8+14 translocation)
Some viral oncogenes have
cellular counterparts
Tumor supressor genes leads to aberrant proliferation, survival, and motility due to
loss of function
Loss of ____ is indicative of a tumor suppressor locus
heterozygosity
___ is a key mediator of epithelial homeostasis, negative regulator of cell cycle progression
TGFbeta
___ is a tumor suppressor gene that is inactivated in many human cancers
p53
p53 can turn on
1) apoptosis
2) sustained G1 and G2 arrest
3) DNA repair
Oncogenes can have gain-of-function by
point mutation, translocation, amplification, overexpression
Tumor suppressor genes can have loss of function by
point mutation, chromosomal loss, deletion, and gene silencing
Have “proofreading” activity
DNA polymerase
Disease that have squamous cell carcinoma susceptability
Fanconi sarcoma
Base excision repair completed by
DNA Pol beta and brought together by DNA ligase
Mismatch repair proteins that are important
MSH2, 6, MLH1
Unwinds DNA
DNA helicase
Removes affected strands
DNA exonuclease
____ can cause intrastrand T-T crosslinks (dimer formation)
UV radiation
Double strand break
break in both strands most likely due to environmental factors
Non-homologous end joining can lead to
1) error
2) translocation
tumor suppressors usually have ___ alleles inactivated
both
Tumor suppressors -inherited mutations predispose to tumor development-
cancer syndromes
Key targets of tumor suppressors
1) cell cycle regulators
2) DNA repair systems