Hallmarks Of Cancer Flashcards
DNA methylation
Promotor methylation = Silencing = repressed expression
Cystine adjacent to Guanine
Epigenetics
Things that change gene expression without changing gene sequence ( factors beyond genetic code)
x2 types of genetic damage
Inherited and Aquired
Aquired genetic damage examples
chemical, microbes,Radiation, spontaneous mutation
Inherited genetic damage
Autosomal dominant + autosomal recessive
Histone Acetylation
promotes gene transcription
At lysine residue of histone
Carcinogen
Substance or agent that causes cancer
Biological, chemical, physical
Biological carcinogen
viruses+ microbes
E-g HPV,EBV, Hep B,Helicobacter Pylori
physical carcinogen
Radiation = chromosomal breakage, translocation, mutation
E.g uv, X-ray, nuclear
characteristics of cancer cells (Hallmarks of cancer)
Self-sufficient in growth signals, Evade apoptosis,insensitive too anti growth signals, Tissue invasion/ metastasis, sustained angiogenesis
Genes which mutation= Tumour x 3
Proto oncogene
Tumour repressor gene
heres involved in DNA repair
carcinogenesis
Multi step process = aquire a series of genetic changes
self sufficient in growth signals
Synthesise & secrete own growth factors = independent of external signals
3 ways to achieve self sufficient growth signals
- Alteration of extracellular signalling
- Alter transcellular transducer (receptor) of specific signal
- Ater intracellular circuit ( signalling proteins)
Insensitivity to growth - inhibitory signals (Rb )
Rb unphosphorylated = E2FS active all time = drives cell cycle
Transforming Growth factor - b (TGFB )
Growth inhibitor
TGFb receptor mutations / unactivation = cells no longer respond to growth inhibitory signals.
How tumours override R-point in mitosis x3
Inactivates TGFb = Less cyclin E
Over-express cyclin E by gene amplification
Inactivates pRb by gene deletion
Evasion of Apoptosis
loss of p53= no longer halts cell cycle during stress conditions
Limitless replicative potential
Produces more telomerase = ability to Proliferate more
chromosome translocation.
Metastasis Steps
Detachment,invasion, intravasation , extravacation, migration
metastasis: detachment
reduction in cell adhesion molecules (CAMS) + E.cadherin = decreased adhesion
metastasis invasion
Release Proteases in Ecm degrades protein in membrane
metastasis intravasation
Tumour cells access arculaction (lymphatic System )
metastasis extravasation
vascular cell adhesion molecule 1 (VCAM_1) facilitates binding to vascular wall
Sustained angiogenesis
Hypoxia = hypoxia induced Factor (HIF.1) increased vascular endothelial growth factor (VEGF) = formation of new blood vessels
spatial+ Temporal Hetrogeneity (tumours)
Spatial = different genetic variation due to region of tumour
Temporal = changes as tumour progresses