Cell and molecular biology of cancer Flashcards
Neoplasm =
Abnormal growth of tissue that usually forms a mass.
A neoplasm arises when…
Balance between cell division, differentiation or death is disrupted.
Benign tumors can still do harm by mechanisms such as
Compression
Factors that favour tumor development:
- genetic instability
- microenvironment inflammation
8 hallmarks of cancer:
- Self-sufficiency in growth signals (oncogenes)
- Insensitivity to antigrowth signals (tumor suppressor genes)
- Evasion of apoptosis
- Replicative immortality
- Sustained angiogenesis
- Invasion of tissue and metastasis
- Reprogramming of energy metabolism
- Evasion of immune destruction
Phases of the cell cycle
G1 G0 S G2 M
Checkpoints in the cell cycle are between
G1 - S
G2 - M
Metaphase - anaphase
Quickest phase of the cell cycle
Mitosis
Name 2 cells that don’t reenter the cell cycle
Neurons
Cardiac myocytes
Main drivers of the cell cycle =
Cyclins and cyclin-dependent kinases
What do CDK-Cyclin complexes do?
Signal stages of the cell cycle
G1 –> S restriction point
In environment favourable?
Is cell bid enough?
DNA damage
G2 –> M transition
Is all DNA replicated?
Is environment favourable?
DNA damage
Ex of external signal
Growth factors
Decribe 2 pathways activated by ATM when DNA damage is detected which act to arrest the cell cycle.
DNA damage - ATM - phosphorylates p53 - increase p21 - p21 inhibits cyclin-CDK - arrest
DNA damage - ATM - phosphylates Chk1/2 - inhibits cdc25 - usually activated cyclin-CDK but is inhibited - arrest
ATM =
Ataxia telangiectasia mutated
p21 acts to
Block Cyclin-CDK complex so cell cycle will arrest
What phosphorylates Rb?
G1-CDK
Rb is usually bound to…
E2F transcription factor
What is mutated in >50% of all tumours?
p53
2 main genes mutated in cancer =
- protooncogenes
- tumor suppressor genes
E2F function =
Transcription factor, DNA synthesis
Proto-oncogenes are mutated to
Oncogenes
Mutations in tumor suppressor need to be…
Both alleles need to be mutated or inactivated to completely inactivate tumor suppressor gene
Ex of oncogenes
Ras
Myc
Ex of tumour suppressor genes
p53
Rb
BRAC 1/2
Oncogenes =
Cause pathways to be switched on inappropriately - excessive proliferation and/or promotion of cell survival
What do oncogenes code for?
- Growth factors
- Growth factor receptors
- Transription factors
- Cell cycle and apoptosis regulators (e.g. CDK 4)
Tumor suppressor genes =
Genes whose loss or inactivation can trigger development of cancer. Usually provice negatice control.
What would increase someones susceptibility to a mutation in a tumor suppressor gene? (hint - retinoblastoma)
Inheriting one mutant allele, only a single mutation can cause a tumor.
Gatekeeper genes =
Directly regulates cell proliferation, loss directly opens the gates to excessive cell proliferation
Ex of gatekeeper genes =
p53
Rb
Caretaker genes =
Maintain genetic stability. Not directly involved with controlling cell proliferation
Ex of caretaker genes
BRCA1, BRCA 2
What normally degraded p53?
Mdm2
What stabalised p53 to increase numbers?
Phosphorylation my ATM
p53 upregulated modulator of apoptosis =
puma protein
Function of Bcl-2
Inhibit apoptosis
Function of puma
p53 - increase puma - inhibits Bcl-2 - Bcl2- usually inhibits apoptosis, apoptosis occurs
HPV infection is found in what % of cervical cancers?
> 90%
HPV produces
Oncoproteins E6 and E7
Function of HPV oncoproteins
E6 = binds to p53, cannot be stabalised if DNA damage
E7 = binds to Rb. Rb not able to sequester transcription factor.
‘2 hit-hypothesis’
Most genes require multiple mutations for a phenotypic change
The 2 hit hypothesis refers to what kind of gene?
Tumor suppressor genes
Ex of cancer with multiple mutations
Colorectal cancer
