Tumour Pathology 4 Flashcards
Define mitosis
a cell division process
What are the phases of the cell cycle
Quiscent:
-G1 : resting phase the cell has left the cell cycle and stopped dicividing. Become dormant. Stimuli can cause these to divide. Eg. in neurons and heart muscle cells
Interphase:
- G1 : cell grows and duplicates contents needed of the S phase.
- S (synthesis) replication of DNA
- G2 : cell grows again in preparation for mitosis
Cell Division:
-Mitosis followed by cytokineses to produce two daughter diploid cells
What external factors control the cell cycle? (4)
Hormones
Growth factors
Cytokines
stroma
What intrinsic factor control the cell cycle?
Checkpoints of the cell cycles
Where are the checkpoints in the cell cycle and what do they control?
G1 checkpoint – ensures everything is ready for DNA synthesis
G2 checkpoint – checks success of DNA replication and ensures everything is ready to enter the M phase
Metaphase checkpoint – during metaphase which ensures cell is ready to divide
Where is the restriction point?
between G1-S phase
the cell requires external factors such as growth factors to pass through the G1 phase. After G1 checkpoint the cells have freedom to divide and do not require growth factors
Where in the cell cycle will the checkpoints be
If cell size is inadequate?
G1 OR G2 arrest
Where in the cell cycle will the checkpoints be
If nutrient supply is lacking
G1 arrest
Where in the cell cycle will the checkpoints be if
Essential external stimuli are lacking
G1 arrest
Where in the cell cycle will the checkpoints be
If DNA not replicated
S arrest
Where in the cell cycle will the checkpoints be
If DNA damage is detected
G1 or G2
Where in the cell cycle will the checkpoints be for
Chromosome mis-alignment
M arrest
What are the checkpoints?
CDKs (cyclin-dependant kinases) are protein kinases that have little activity. They require the molecule cyclin to bind to it and hence the CDK/cyclin complex is now activated kinase enzyme
How do CDKs/Cyclins control the cell cycle?
Different CDKs and cyclins operate at different stages and they phosphorylate substrates which can activate or deactivate the substrates
The activation/deactivation of substrate regulates events in cell cycle
How can CDK activity be regulated?
Cdks are expressed in an inactive form
cyclins accumulate and are destroyed as the cycle progresses
What are the two inhibitors of the CDK complex?
INK4A family
CIP/KIP family
What do the inhibitors of CDK do?
They bind to the CDK and prevent it from binding to cyclin
How does the retinoblastoma gene inhibit the cell cycle?
retinoblastoma gene is a tumour suppressor protein that binds the E2F transcription factor and inhibits cell cycle entry when its hyperphosphoralated
What happens when the CDK/ cyclin D complex phsophorylates the retinoblastoma gene?
When CDK4/cyclin D complex phsphoralates the retinoblastoma (pRb) it loses affinity for the E2F trascription factors.
The free E2F stimulates cell cycle entry
What is carcinogenesis?
The process in which a cell turns cancerous
What causes the cell cycle to lose control and proliferate?
Mutations in genes regulating cell division, apoptosis and DNA repair
What enviromental factors cause carcinogenesis?
Chemical
Radiation
Oncogenic viruses
Explain how chemical factors can cause carcinogenesis
Various oxidising and alkylating agents damge DNA bases and react with DNA forming DNA adducts and this causes cancer
Explain how radiantion can cause cancer
DNA bases get damaged radiation eg. x-ray, UV and Gamma radiation
