Lecture 15: cancer 33 Flashcards
(38 cards)
Identified tumour suppressor genes:
- Rb
- P53
- WT-1
- Ptc
- BRCA-1
- APC
Inherited cancer predisposition diseases
- Retinoblastoma
- Li Fraumeni
- Wilm’s tumour
- Gorlin’s syndrome
- Breast cancer
- Familial adenomatous polyposis coli (FAP)
Oncogenes vs tumour suppressor genes: number of alleles mutated to exert effect
oncogenes: one
TSG: 2
Oncogenes vs tumour suppressor genes: effect on the function of the protein
oncogene: Enhanced
TSG: reduced
Oncogenes vs tumour suppressor genes: inherited mutations:
oncogenes: RET, Abl
TSG: p53, RB, WT-1, Ptc, APC
Oncogenes:
activate, gain of function, dominant
TSG:
inactivating, loss of function, recessive
normal cell division, normal apoptosis:
HOMEOSTASIS
INCREASED cell division, normal apoptosis :
TUMOUR
Normal cell division, DECREASED apoptosis :
TUMOUR
cell cycle
G1 - growth 1
S - replicate genome
G2 - growth phase 2
M - cell division
Many genes control cell division:
- Many Genes Promote Cell Division
- Many Genes Block Cell Division
DNA detected by stable, active p53
- Hyperproliferative signals
- DNA damage
- Telomere shortening
- Hypoxia
outcome from p53 detecting DNA damage
- cell cycle arrest
- senescence
- apoptosis
p53 has been called the
‘guardian of the genome’
p53
• arrests cells when DNA is damaged
• turns on transcription of DNA repair genes and
genes that arrest cell cycle
• turns on apoptosis when all else fails
many cancers arise from defects in the machinery that regulates
cell growth and/or cell death
most cancer cells are defective in apoptotic response
⇑anti-apoptotic or
⇓ pro-apoptotic proteins
CANCER
Cancer cells have tricks to avoid apoptosis:
B-cell leukemias and lymphomas express
high levels of Bcl-2
Cancer cells have tricks to avoid apoptosis: Lung and colon cancer cells
secrete
“decoy” molecules that bind and inactivate MHC type1 receptors
⇓T cell recognition sites
—Cytotoxic T-lymphocytes & NK cannot kill the cancer cells
routes of tumour spread
- direct
- via lymphatics
- transcoelomic
- field change
- via bloodtsream
Metastasis mechanism
still poorly understood
metastasis is promoted by
- ⇓ adherence between cells
- Synthesis of defective basement membrane
- Tumour angiogenesis
- ⇑cell motility
- Secrete growth factors
- Secrete alternative extracellular matrix
- Secrete proteinases
- Evade host immune system
treatment for cancer:
- Surgery
- Radiotherapy
- -Chemotherapy
- Endocrine-related treatments
- Immunotherapy
- –Interferons, vaccination
- Molecular mechanism-based