Cell Cycle and Cancer Flashcards
What does the cell cycle do?
- somatic cells need to replicate and divide therefore the cell cycle allows them to grow and repair
- it ensures genetic integrity
- duplicates the contents of the cell
- involved in cellular differentiation
- a multi step process that proceeds sequentially and is tightly controlled
What are different features in the cell cycle?
- defined steps “checkpoints”
- distinct control mechanisms
- regulated by protein complexes that work in a specific order
What are the 4 phases of the cell cycle?
- G1
- S
- G2
- M
- each phase has its own distinct functions
What is G1 phase and what does it use?
- first phase of cell cycle
- start considered to be the point prior to DNA replication
- regulated by “G1 CDK:cyclins” which serve to initiate E2F transcription factors
- E2F target genes encode proteins required for DNA replication (DNA polymerase, nucleotides, etc)
How does G1 E2F become activated?
- E2F’s default setting is off which is controlled by pRb
- to activate E2F, the effect of pRb is negated by CDK:cyclins
- mitogenic stimulation increases cyclinD-CDK4 which phosphorylates pRB to allow the release of E2F
How can G1 CDK be inhibited?
- cells have an intrinsic ability to counteract the go signal elicited by CDKs
- without this, cells would grow forever
- endogenous inhibitors are activated by cytokines
- they are increased in response to DNA damage and are able to halt cells
What happens at the G2/M checkpoint?
- there are not many checkpoints in G2/M transit
- the cell is assumed to be okay if it has gotten this far
- CyB-CDK1 ensures cells are ready for splitting by checking correct alignment of chromosomes and the integrity of spindle fibres
- faults at this point are terminal and are dealt with by mitotic machinery
What happens if the cell shows problems at the G2/M checkpoint?
- checkpoint is between transition from metaphase to anaphase
- if chromosomes do not align properly or spindle fibres don’t connect the cells could become cancerous
- mitotic catastrophe can induce cell death to dispose of these cells to ensure their quality
What happens if the cell shows problems at the G2/M checkpoint?
- checkpoint is between transition from metaphase to anaphase
- if chromosomes do not align properly or spindle fibres don’t connect the cells could become cancerous
- mitotic catastrophe can induce cell death to dispose of these cells to ensure their quality
What is G0?
- the cell cycle is primarily associated with active proliferation
- however, a large proportion of cells lie dormant and are said to be in G0
- these cells:
- contain 1 set of DNA
- don’t actively divide
- are resistant to death
- can re enter cycle
How can the cell cycle be tracked?
- cells stained with a DNA dye
- flow cytometry is used to asses the DNA content of individual cells
- peaks formed indicated different stages of the cell
- DNA profile can also inform the state of the cell (eg if its polyploidy or undergoing apoptosis)
How do cells become polyploids?
- cell has been manipulated to express cells with abnormal ploidy
- polyploidy is when cells contain more than 2 sets of any of the chromosomes
- occurs when cells lose the G2/M transit checkpoint
- they need to divide before they can move to S phase
How is hyper proliferation caused?
- faults can trigger checkpoints whose job is to brake cell cycling
- loss of control of the cell cycle leads to uncontrolled proliferation which can result in cancer
- mutations in the cell cycle result in a direct loss of regulatory function
What are 3 mutations that cause hyper proliferation?
- Decreased p16 = increased cyD-CDK4
- Decreased pRb = increased E2F
- Decreased p53 = decreased p21 = increased CDKs
How do drugs target cell cycle mutations?
- there are a number of ways to prevent cancer cells from growing:
1. Counteract the “keep growing” signal
2. Neutralise the “don’t die” signal
3. Induce a “die” signal
4. Disrupt the normal cell cycle processes - drugs that perform these roles are:
1. Anti-proliferatives
2. Anti-metabolites
3. Cytotoxics
Why should we track the cell cycle?
- allows a better understanding of what drugs are doing and how they work
- find ways to improve treatments
What can treatments do to the cells?
Cytotoxicity:
- interfere with replication
- disturb alignment of chromosomes
- cause certain cancer cells to die
Cytostasis:
- inhibition of cell growth beyond G2
- prevents transition from G2 into M phase
- doesn’t necessarily cause cell death
Recovery:
- treatments in the future could allow cells to recover instead of killing them completely
