Flashcards in tumour pathology 4 Deck (27)
what is a cell cycle?
the interval between mitotic divisions
what are the phases of the cell cycle, and what happens in each?
1. G1 - synthesis of components required for DNA synthesis
2. S - DNA synthesis
3. G2 -preparation for mitosis
4. M - mitosis and cell division
G0- extension of G1, quiescent state, dormant
when does DNA repair occur?
when can the cell cycle be affected by external factors?
in the G1 phase
examples of external factors
hormones, cytokines, growth factors, stroma
where are the checkpoints of the cell cycle?
-G1 checkpoint at the G1/S transition
-G2 checkpoint at -the G2/M transition
-M checkpoint between metaphase and anaphase
where is the cell cycle arrested if cell size is inadequate?
G1 or G2
where is the cell cycle arrested if nutrient supply is inadequate?
where is the cell cycle arrested if essential external stimuli are lacking?
where is the cell cycle arrested if DNA is not replicated?
where is the cell cycle arrested if DNA is damaged?
G1 or G2
where is the cell cycle arrested if chromosomes mis-align
how do checkpoints work?
1. cyclin dependent kinases are present in the cell
2. cyclin levels rise if the checkpoint has the go-ahead.
3. these bind to CDKs, activating them.
4. the active CDKs then act by phosphorylating sybstrates
5. these phosphorylated substrates are required for the next stage of the cell cycle
the cell cycle is also regulated using CDK inhibitors
what does INK4A inhibit?
what does the retinoblastoma gene encode for?
when is pRb active?
when it is hypophosphorylated
when is pRb inactive?
when it has been phosphorylated by cyclin D/CDK complexes
what is the function of pRb?
E2F transcription factor, this activates vital target genes for the stimulation of cell cycle entry
how do oxidising and alkylating agents cause carcinogenesis?
they critically damage purine and pyrimidine bases in DNA
what is a DNA adduct?
covalently bound products of DNA and a chemical carcinogen
how does radiation damage DNA?
damages the purine and pyrimidine bases
types of ionising radiation
-UV (UV-B in sunlight)
what are the two regulatory pathways regularly disrupted to cause cancer?
1. The cyclin D-pRb-E2F pathway
2. p53 pathway
which checkpoint is usually dysregulated in cancer cells and which four genes are mutated?
Rb, CDK4, cyclin D and p16