Tumour Pathology 4 Flashcards
(38 cards)
What do disorders of cell growth include?
- Normal and abnormal cell cycles
- Chemical carcinogenesis
- Radiation carcinogenesis
What is mitosis?
The mechanism of cellular replication and involves nuclear division plus cytokinesis
What does mitotic division generate?
Two genetically identical daughter cells
What is the cell cycle?
The time interval between mitotic divisions
What are the phases of the cell cycle?
- G1
- S
- GS
- M
What is tightly controlled during mitosis?
Production of cell numbers and cell types
What must a cell do to produce viable progeny?
Progress through cycle phase in the correct sequence
What must occur sequentially/
DNA synthesis and mitosis
What is ensured during quality control of cells?
- Genetic fidelity in daughter cells
- Each cell must receive a full chromosome complement
- Mutations in DNA sequence must not pass on
What are the external factors in cell cycle control?
- Hormones
- Growth factors
- Cytokines
- Stroma
What are the intrinsic factors in cell cycle control?
Critical checkpoints including restriction point (R)
- Prior to R, progress through G1 depends on external stimuli
- After R progression becomes autonomous
Cell cycle checkpoints: If cell size inadequate…
G1 or G2 arrest
Cell cycle checkpoints: If nutrient supply inadequate…
G1 arrest
Cell cycle checkpoints: Essential external stimulus lacking…
G1 arrest
Cell cycle checkpoints: If DNA is not replicated
S arrest
Cell cycle checkpoints: If DNA damage is detected
G1 or G2 arrest
Cell cycle checkpoints: Chromosome mis-alignment
M-phase arrest
What are checkpoints?
A system of cyclically active and inactive enzymes
How are checkpoints activated?
Catalytic sub-unit activated by regulatory sub-unit
What are the sub-units called?
- Catalytic sub-units are called cyclin-dependent kinases (CDKs)
- Regulatory sub-units are called cyclins
- The active enzyme complex= CDK/cyclin complex
How CDKs work?
- Different CDKs and cyclins operate at sequential stages of the cycle
- Active CDK/cyclin complexes phosphorylate target proteins
- Phosphorylation results in activation/inactivation of tat substrate
- Substrates regulate events in the next cycle phase
How is CDK activity regulated?
- CDKs are constitutively expressed in an inactive form
- Cyclins accumulate and are destroyed as cycle progresses
- Regulation is exerted by CDK inhibitors (CKIs)
What examples of CKIs are there?
- INK4A family bind to CDK4 and 6 and prevent association of these CDKs with their cyclin regulatory proteins (p16INK41) (p15ink4B) (p18INK4C)(p19INK4D)
- Second family of CKIs- CIP/KIP family p21CIP1
- These inhibitor molecules bind to cyclin/CDK complexes
Describe how the retinoblastoma gene works.
-Encodes a 110 kDa phosphoprotein (pRb) expressed in almost every cell of the human body
-pRb is hypophosphorylated
-Phosphorylation increases as cells progress through the cell cycle
Active cyclin D/CDK complexes phosphorylate pRb
