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