Tumour Pathology 4 Flashcards
What is the G1 or G2 Arrest for?
To check it cell size is adequate.
If DNA damage is detected.
What is the G1 arrest for?
Check if the nutrient supply is adequate.
If the essential external stimulus is lacking.
What is the S arrest for?
If the DNA is not replicated.
What is the M phase arrest for?
If there is chromosome misalignment.
What catalytic and regulatory subunits make up an active enzyme complex for checkpoints in mitosis? Which one is sequential?
Catalytic subunit is cyclin dependent kinase (CDK)
Regulatory subunit is cyclin.
Make up active enzyme complex CDK/cyclin complex.
CDK is always expressed while cyclin is sequentially expressed.
What are two families of CDK inhibitors and how do they work?
INK4A binds to CDK4 and 6 and prevents association of these CDK by producing regulatory proteins like p16.
CIP/KIP bind to the active enzyme and produce p21.
What does the retinoblastoma gene encode for? What is this phosphorylated by?
Encodes a 110 kDa phosphoprotein (pRb) which is hypophosphorylated. It is phosphorylated by cyclin D/CDK complexes.
What affinity does pRb have for E2F transcription factor and what effect does this have on the cell cycle?
Hypophosphorylated/active pRb inactivates E2F.
Phosphorylated/inactive pRb loses affinity for E2F.
E2F is a potent stimulator of cell cycle entry and activates vital target genes. So activation of pRb puts the brakes on the cell cycle.
What are two commonly disrupted cell cycle pathways in carcinogenesis?
Cyclin D-pRb-E2F pathway so the pRb gets mutated so it can’t put a brake on the cell cycle.
P53 pathway is mutated means that there is no G1 arrest or damage repair for DNA.
How do chemicals affect DNA and cause carcinogenesis? (Radiation similar)
They affect the pyrimidine and purine bases of the DNA and critically damage them. They or their active metabolites reach with DNA and from covalently bound products (DNA adducts). Adduct formation causes oncogene expression.
What four genes are most commonly mutated in cancer?
CDK4
pRb
Cyclin D
p16
How do oncogenes develop from Proto-oncogenes?
The proto-oncogenes can be altered structurally by point mutation or by chromosome rearrangement/translocation.
The proto-oncogene expression can be dysregulated by gene amplification or overexpression.
How can viruses cause carcinogenesis?
A virus genome can insert itself near a host proto-oncogene and a viral promoter can cause proto-oncogene overexpression.
What are three DNA viruses known to cause cancers and what type of cancers are they?
HPV causes cervical cancer.
Hepatitis B causes liver cancer.
EBV causes burkitts lymphoma. (Epstein-Barr Virus)
