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MM22 Cancer Cell Biology 1 (i) (cancer (can be classified according to…
MM22 Cancer Cell Biology 1 (i)
cancer
excessive cell division due to failures in mechanisms maintaining normal cellular growth rates
loss of growth regulation due to genetic damage of regulatory genes
<10% inherited (e.g. BRCA1 mutation)
most due to environment
200 types
causes 20% of disease related death
huge burden: 40% of people get cancer @ some point
can be classified according to origin
carcinoma: epithelial cells (eg lung, hepatic, melanoma) - 90% of cases
sarcoma: mesodermal cells (eg osteosarcoma, rhabdomyosarcoma) rare
lymphoma (lymphoid tissue) / leukaemia (WBCs): cells in blood + lymphatic system (e.g. myeloma - plasma cells/B cells)
neoplasm
new growth
benign = localised, grows by expansion, can compress/displace surrounding tissue
malignant = capable of invasion + metastasis, grows by local infiltration, can destroy surrounding tissue
Models for tumour propagation
clonal evolution model
mutant tumour cells with a growth advantage are selected + expanded
natural selection, increased aggression (evolution)
older model
all cells in dominant pop have similar potential for initiating tumour growth
each successive mutation gives cell a growth advantage
Cancer Stem Cell/tumour cell initiation model
only a rare subset of tumour cells have the ability to self renew + generate diverse tumour cells (i.e. cancer stem cells)
tumours a heterogenous + hierarchal
tumours are composed of CSCs + cells that arise from CSCs but can't initiate tumours (Transit-amplifying cells)
CSC frequency is highly variable (often low)
CSCs have ben identified in most cancers, but not all
CSCs can self renew -> NB for initiation + long term maintenance of tumour
Transit-amplifying cells can expand tumour, but not for longterm maintenance
both models account for tumour heterogeneity + differences in regenerative capacity
both models are not mutually exclusive
e.g. CSCs may undergo clonal evolution
Mutations in 3 classes of genes can cause cancer
protooncogenes
promote cell proliferation
gain-of-function-mutation: excessively active
1 mutant allele may affect phenotype
tumour supressor genes
inhibit cell proliferation + promote apoptosis in damaged cells
usual 2 mutant alleles needed, but sometimes only 1 (haploinsufficiency)
e.g. Rb, P53, APC, BRCA1
care taker genes
ensure accurate replication, repair, segregation
mutation: genomic instability
e.g. in mlh1 + msh2 (MMR genes)
wildtype allele
most common in pop
usually unmutated