The cell cycle I Flashcards
What are 5 causes of cancer?
What are examples?
1) Environmental/carcinogens
2) Viral infections (Rous Sarcoma virus)
3) Inherited factors (Retinoblastoma)
4) Genetic instability (Oncogenes and tumour suppressor genes)
5) Defects in the machinery that regulate normal cell growth/cell death (genes promoting/blocking cell division)
What causes cells to proliferate?
EXTRINSIC factors
What 2 things can cause the halt of cell proliferation?
1) The ABSENCE of the extrinsic factors due to blockage by other signalling pathways
2) Induction of a POST-MITOTIC, differentiated state where no proliferation occurs
What is the ‘cell cycle clock’?
Master governor that operates in the nucleus and and makes the major decision of whether to: proliferate, be quiescent or differentiate
Network of interacting proteins (CDKs and cyclins)
How does the cell cycle clock make the decision on if to proliferate, be quiescent or differentiate?
Receives and integrates signals from the OUTSIDE and the INSIDE of the cell
What happens if the cell cycle clock makes the decision to proliferate?
Cell goes through cell cycle of growth and division
What happens if the cell cycle clock makes the decision to quiesence?
Cells go into a non-proliferative state (G0)
What must occur between neighbouring cells when cells decide to grow or become quiescent?
Why?
The cells must ‘consult’ neighbouring cells
There are many different types of cells in a tissue - proliferation must be coordinated between the cells
How do cells communicate to their neighbours to tell them if they are proliferating?
Through GROWTH FACTORS
What are growth factors?
Small proteins that are RELEASED by cells
Travel through the extracellular matrix
Convey messages to OTHER cells
What are growth factors also called?
Why?
Mitogens
This name indicates the ability of the GFs to be able to induce cells to proliferate
What do virtually ALL cells need in order to grow and divide?
Which cells are the exceptions? How?
GF signals
Exceptions: embryonic stem cells
Mouse ES cells shown to drive their own proliferation through INTERNALLY GENERATED signals
What are the ONLY examples of WT cells that can induce a benign tumour in an adult organism?
What is this cancer called?
ES cells
Cancer - teratoma
Why are the external signals required when a cell is proliferating?
To maintain the precise STRUCTURE and INTEGRITY of the tissue in which the cells are located
What does uncontrolled proliferation lead to?
The formation of a tumour
What happens to the cell cycle clock in cancer?
It becomes influenced by cancer-associated proteins (oncogenes, tumour supressor genes)
Which DISRUPT the NORMAL control mechanisms
And lead to SUSTAINED cell proliferation
What are 5 ways in which sustained proliferation can occur?
1) Production of GF by themselves (autocrine stimulation)
2) Signals to SURROUNDING cells to produce MORE GF
3) DeREGULATION of downstream GF receptors
4) Constitutive ACTIVATION of signalling downstream of GF receptors
5) Disruption of the NEGATIVE FEEDBACK mechanisms that normally reduce proliferative signalling
What are GF produced by?
The STROMA around cells
What does the deregulation of downstream GF receptors cause?
Elevated level of receptors
Ligand-independant firing
What does the constitutive activation of signalling downstream of growth factors cause?
GFR become independant of the the ligand in the environment
What does the disruption of negative feedback mechanisms cause?
Increase in proliferative signalling (negative feedback normally acts to reduce the signalling)
What is the major difference between the growth of normal cells and the growth of cancer cells?
Normal cells ONLY grow in the presence of GF
Cancer cells can grow either in the presence or absence of GF
What happens to the cells when they proliferate?
Go through the cell cycle and division
What is G0?
Where do cells enter G0 from?
The NON-GROWING (quiescent) state of the cell cycle
Cells enter from G1
Why do cells enter G0?
Due to the ABSENCE of GF
OR
The PRESENCE of growth INHIBITORS
What is an example of a growth inhibitor?
TGFb
When cells are in G0, what 2 things can happen?
Describe these
Stay REVERSIBLY - Mitogens can re-stimulate cell proliferation
Stay IRREVERSIBLY - Post-mitotic cells
Where does the decision of the cell to undergo proliferation or quiescence occur?
In the G1 phase of the cell cycle
What happens the cell decides to proliferate?
What is this process called? What is this different to?
DOUBLING of the cells macromolecular constituents - ACCUMULATION oft the cellular constituents
Called CELL GROWTH - Different to cell DIVISION
What happens in S phase?
DNA is REPLICATED
What is the length of S phase determined by?
The AMOUNT of DNA needed to be replicated