Cells and molecular biology of cancer Flashcards
tumour=
abnormal growth of tissue that usually forms a mass
what is the cause of all cancer
genetic mutations
when do tumours arise
when balance between cell division and cell differentiation or death is disrupted
what cells do genetic mutations causing cancer have to be in
proliferating cells
what gene mutations are in most tumours
genes controlling cell cycle
5 stages of cell cycle
M G0 G1 S G2
interphase=
G1, G2, S (synthesis)
Gap 1 (G1)=
no visible changes but increase in cell contents (organelles, proteins ect)
Synthesis=
replication of DNA occurs, resulting in chromosomes becoming 2 sister chromatids
G2=
preparation for division process
g0=
not going through cell cycle
what ensures the cell cycle is happening in the right order
cyclin- CDK
what does cyclin- CDK do
signal stages of the cell cycle to happen
what controls cell cycle progression
transition points
what halts the cell cycle if the cell is unsuitable
checkpoint pathways
when is cyclin level highest in the cell
in mitosis
restriction point at_______
G1–> S
3 checkpoints in cell cycle
- DNA damage checkpoint
- DNA replication checkpoint
- Mitotic spindle checkpoint
what causes external signalling
growth factors
internal signalling for the cell cycle can happen because of
DNA damage
p53=
transcription factor
what 2 proteins have a kinase activity and activate DNA repair and p53
ATM and ATR
what happens to p53 after DNA damage
phosphorylation by ATM making p53 go into the nucleus and stimulate expression of many genes including p21
what does p21 do
an inhibitor of cyclin and CDK leading to cell-cycle arrest
what do most proto-oncogenes code for
components of the regulatory pathways of growth/ cell division
how many mutations can enable oncogenes
1- mutation in one allele
how many mutations in tumour suppressors genes to inactivate them
2- mutations in both alleles
5 types of gene mutation
- point mutation
- gene amplification
- chromosomal translocation
- local DNA re-arrangement
- insetional mutagenesis
2 main classes of tumour suppressor genes
caretakers and gatekeepers
e.g of 2 gatekeepers
Rb
p53
what does Rb control
G1—>S restriction point
loss of gatekeeper causes
excessive cell proliferation
caretakers—>
maintain genetic stability (e.gDNA repair) but not directly involved in controlling cell proiliferation
e.g of caretaker
BRCA1 and 2
when a cell detects DNA damage levels of what normally increase
p53
where does p21 arrest the cell cycle
G1
if there is no p53 what happens
cell will carry on the cell cycle even with DNA damages
what instructs the DNA repair proteins to start repairing
ATM
what usually keeps p53 at low levels
because its bound to Mdm2 which keeps its levels low via degradation
what does Rb regulate
a transcription factor (keeping it away from the nucleus) which would otherwise start the expression of genes making the cell progress into the G1 phase
what happens in tumours without Rb
transcription factor is always free to bind the DNA—> lots of proliferation
what does viral factor E7 produced from HPV do
E7 binds to Rb and keeps it away from the transcription factor
what does viral factor E6 produced from HPV do
sequesters p53 so it can no longer stop the cell cycle when DNA needs repair
