Tumour Pathology 4 Flashcards
What is quiescence?
Rest phase of cell cycle; nothing is happening
What external factors control the cell cycle?
Hormones, growth factors, cytokines
What intrinsic factors control the cell cycle?
Critical checkpoints - restriction point (R)
Prior to restriction point, progress through G1 depends on what factors?
External
After restriction point progression of the cell cycle is ________
Autonomous
At what points in the cell cycle are there checkpoints?
G1, G2 and M
What are the cell cycle checkpoints?
System of cyclically active and inactive enzymes - catalytic sub-unit activated by a regulatory sub-unit
Catalytic sub-units are known as what?
Cyclin-dependent kinases (CDKs)
Regulatory sub-units are known as what?
Cyclins
What is the active enzyme complex comprised of regulatory and catalytic subunits?
CDK/cyclin complex
What is the purpose of active CDK/cyclin complexes?
Phosphorylation of target proteins resulting in their activation/deactivation
How is CDK activity regulated?
CDKs are expressed in an inactive form and as cyclins accumulate they are destroyed as the cycle progresses
What two families of CDK inhibitors (CDKis) are important to checkpoints?
INK4A family and CIP/KIP family
The imbalance of what two natural processes results in carcinogenesis?
Cell proliferation and apoptosis
Chemical carcinogens (or their active metabolites) react with DNA forming covalently bound products called what?
DNA adducts
Adduct formation at particular chromosome sites causes what?
Cancer
What type of UV-light causes cancer?
UV-B
What is the primary defect in cancer?
Uncontrolled cell proliferation via cell cycle dysregulation
What are two regulatory pathways frequently disrupted in cancer?
- The cyclin D-pRb-E2F pathway
2. p53 pathway
Virtually all cancers are dysregulated at what stage because of mutation?
G1 to S
Dysregulation at the G1-S stage is usually due to a mutation in which four potential genes?
Rb, CDK4, cyclin D and p16
What are the functions of p53?
Maintains genomic integrity
Increased levels in damaged cells:
Induces cell arrest at G1
Facilitates DNA repair
Severe damage: p53-induced apoptosis
