The cancerous cell Flashcards
What are the hallmarks of cancer?
Evading apoptosis
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion & metastasis
Limitless replicative potential
Sustained angiogenesis
What are major cellular processes affected in cancer development?
1) Cell cycle
2) apoptosis is reduced
3) cell adhesion is impaired - tumour cells can detach
4) angiogenesis - deliver oxygen & nutrients to tumour
What are the checkpoints of the mammalian cell cycle?
G1 - favourable environment?
G2 - DNA replicated? favourable environment?
Metaphase - chromosomes attached to spindle?
What are types of mutations that occur in cancer?
point
amplification
deletions
chromosomal rearrangements
What can expression of genes be influenced by?
- methylation of specific C in promoters
- Chromatin remodelling, post-trans mods in histones
What are the 3 main genes involved in cancer?
Oncogenes
Tumour suppressor genes
Genes involved in DNA repair
What is a dominant cancer mutation?
single mutation event in proto-oncogene
creates oncogene
enables oncogene to stimulate cell proliferation
What is recessive cancer mutation?
mutation event - inactivates tumour suppression gene
2nd mutation even inactivates second gene copy on chromosome
suppressor gene eliminated
What are the 3 ways a proto-oncogene is converted?
mutation in coding sequence
Gene amplification
Chromosome rearrangement
What are functions of the proto-oncogenes?
Growth factors
Growth factor receptors
Signal transducers
Nuclear proto-oncogenes & transcription factors
What is retinoblastoma?
eye cancer caused by a mutation in a tumour suppressor gene
can be hereditary as can inherit once mutant Rb gene already - only 1 more to mutate
What happens when Rb (of retinoblastoma) is mutated?
doesn’t bind to transcription factor E2F
constant activation and progression of cells into S phase
What are the virus oncogenes of HPV16?
E6 and E7 - highly growth promoting
E7 binds it and targets it for degradation
p53 - tumour repressor frequently mutated
E6 bind to p53 and degrade it
What is a bacteria associated with gastric cancer?
Helicobacter pylori
elimination of H pylori by antibiotics reduces gastric cancer
chronic inflammation of gastric mucosa
What can DNA replication errors be detected by?
MutS and MutL
What are the stages of colon cancer
Small adenoma
Large adenoma
Carcinoma
Inherited colon cancer account for what %?
10-15%
mutations in hereditary are similar to those in sporadic
What is familial adenomatous polyposis?
0.01% colon cancer
single gene disorder
truncation mutations in APC protein
What is HNPCC?
mutations in mis-macth repair enzymes hMLH1 and hMSH2
polyps fewer than FAP
