carcinogenesis Flashcards
what are the different genetic legions that could be present in cancer?
amplification deletion point mutation translocation epigenetic changes
amplification
increases expression of of growth promoting genes
translocation
generates fusion proteins with altered function
point mutation
creates proteins with affected constitutive cell signaling capacities
deletion
affects growth inhibiting and dna repair genes
epigenetic changes
reversible changes in gene expression
how do miRNAs contribute to carcinogenesis?
regulating expression of growth/survival/death genes
carcinogenesis involves four classes of growth regulatory genes what are they?
proto oncogenes
tumor suppressor
dna repair
genes regulated programmed cell death
when oncogene mutated what does it form?
oncogene
oncogenes function
deregulate growth promoting signals = tumor cell in control of growth
in normal conditions whats the role of an activated RAS?
when cell stimulated through GF receptor transduce proliferative signals to nucleus
what happens in RAS oncogene / mutation in RAS?
constituitive signalling of pathway without a growth factor
over expression of EGF (epidermal growth factor receptor)
breast lung and other tumors
constitutive activation of signaling molecules downstream the receptors –> BRAF
melanoma + thyroid cancer
constitutive activation of signaling molecules downstream the receptors –> ABL
chronic myeloid leukemia
constitutive activation of signaling molecules downstream the receptors –> beta catenin
liver cancer
overproduction / unregulated activity of transcription factor C-MYC
lymphoma
mutations that activate cyclin genes / inactivate negative regulators of cyclin and cyclin dependent kinases ( CDK and CDK inhibitor) result it …
uncontrolled cell cycle progression
mutations that activate cyclin genes / inactivate negative regulators of cyclin and cyclin dependent kinase are ass with
melanomas
brain lung and pancreatic cancer
what does G2/ m checkpoint check?
dna replicated
dna not damaged
Go checkpoint
mitogens and antimitogenic and differentiation signals
G1/S checkpoint
size
dna damage
what detects dna damage and inhibits cell cycle at G1 and G2?
p53
lifraumeni syndrome
inherited p53 mutation –> predisposition to breast cancer sarcomas and other neoplasms
what controls G1/S transition>
RB gene
retinoblastoma
2 mutated RB genes lead to neoplastic proliferation of retinal cells
what are the four key cell cycle regulators?
Rb
CDKN2A
cyclin D
CDK4
what are the mechanisms used by the tumor cell to evade death
reduced c95
inactivate death induced signaling complex
BCL2 up regulation causing reduced release of cytochrome c from mitochondrion
reduced levels of apoptotic BAX
loss of of APAF-1
upregulation of inhibitors of apoptosis
proangiogenic factor
VEGF ( if elevated poor prognosis and increased risk of metastases)
BRCA1 and 2
dna repair genes mutated in breast cancer
dna mismatch repair pathway mutated in…
hereditary nonpolyposis colorectal cancer (HNPCC)
nucleotide excision repair pathway mutated in …
xeroderma pigementosum
what cytokines stimulate tumor cell motility and EMT?
TNF annf TGF beta
what is used to treat colonic adenomas?
COX2
x ray workers
leukemia
radio isotopes
thyroid carcinoma
atomic explosion
skin cancer
leukemia
polycyclic hydrocarbons
lung cancer
aromatic amines and azo dyes
carcinoma of the bladder
HTLV1
T cell leukemia /lymphoma
HPV
carcinoma of cervix
HBV and HCV
primary hepatocellular carcinoma
EBV
lymphoma
nasopharyngeal carcinoma
HHV 8
kaposi sarcoma
helicobacter pylori
gastric cancer
