L14(Cancer) Flashcards
(30 cards)
Cancer
divserse set of genetic diseases that share some common features
- somatic cells accumulate mutations in variety of genes
- mutations cause cancer cells to divide rapidly and uncontrollable
Hallmarks of cancer
- Promote cell growth
- Resist apoptosis(cell death)
- Evade growth suppressors
- Inducing angiogenesis(formation of blood vessels)
- Invasion of other cells and metastasis
- Replicative immortality
p53 protein
“guardian of genome”
- regulates cell cycle, DNA replication, apoptosis
example of mutation in p53:
- Li-Frameni syndrome: 100% breast cancer, 90% other cancers, autosomal dominant pedigree
Environmental factors in cancer
- Radiation
- Tobacco
- Obesity
- Chemicals
- UV
- polycyclic aromatic hydrocarbons(PAHs)
Tumor formation
distinct mass of abnormal cells
benign tumors: tumor remains localized
malignant tumors: tumor cells invade other tissues/metastasize
metastasis: tumor cells induce secondary tumors
Cancer as a genetic disease
Genetic evidence of cancer: karyotypes, chromosomal abnormalities, inheritance
Knudsons multistep model of cancer:
- first hit: tumour develops in germline suspectibility gene
- second hit: occurs somatically in other allele of same gene
Clonal mutation of tumors: tumor cells acquire more mutations, become increasingly aggressive
Mutations in types of genes contribute to cancer
- oncogenes and tumor suppresor genes
- genes that control cell cycle
- DNA-repair genes
- telomerase genes
- genes that promote vascularization
Proto-oncogenes and oncogenes
Proto-oncogenes: responsible for basic cellular function in cells
Oncogenes: mutated versions of proto-oncogenes, stimulatory genes that cause cancer
Tumor suppresor genes
- non-mutant reduces cell growth
- mutated inhibitory recessive genes that are inactive
- loss of heterozygosity(loss of control in inhibiting cell growth)
- mutated in both alleles or deletion in one allele to cause cell proliferation
Examples of proto-oncogenes
- erbB: growth factor receptor, many types of cancer
- fos: transcription factor, osteosarcoma and endometrial carcinoma
- jun: transcription factor, cell cycle control, lung and breast cancer
- myc: transcription factor, lymphomas, leukemias, and neuroblastoma
- ras: GTP binding/GTPase, many types of cancer
- sis: growth factor, glioblastomas and other cancers
- src: protein tyrosine kinase, many types of cancers
Example of tumor suppresor genes
- APC: scaffold proteins, microtubule interaction, colorectal cancer
- BRCA1: DNA repair, transcription factor, breast and ovarian cancer
- CDKN2A: regulates cell division, melanoma
- NF1: GTPase activator, neurofibromatosis
- p53: regulates cell division, etc., many types of cancer
- RB: regulates cell division, retinoblastoma, other types of cancer
Cancer genome projects
help strategize treatments
Epigenetic changes associated with cancer
alterations to DNA methylation or chromatin structure
- hyper/hypo methylation
Ways cancer evades controls on cell growth
- produce cell division signal(autocrine stimulation)
- lose contact inhibition
- avoid apoptosis
Angiogenesis
- produce substances that encourage blood vessel growth
- blood vessels provide nutrients to tumors, allows metastasis(movement to other locations)
- evade immune surveilance
Viruses associated with cancers
retroviruses cause cancer by mutating and rearranging proto-oncogenes, inserting strong promoters near proto-oncogenes
eg. human papilloma virus and cervical cancer
Cancer associated with age
Cancer rises dramatically with age. supports idea that cancer involves accumulation of mutations in clonal descendants of a somatic cell
Passenger and driver mutations
majority of mutations in cancer genomes are passenger mutations(occur due to increased mutation rate, do not contribute to disease)
driver mutations: cause cancer phenotypes, several driver mutations in different genes must accumulate for cancer to result
Control of cell division
Growth factors: mitogens stimulate cell proliferation
Receptors: bind growth factors, initiate signal transduction cascade, activates synthesis of transcription factors
Transcription factors: regulate genes whose protein products cause cells to divide/stop dividing
Necessity of checkpoints
checkpoints prevent transmission of genomic instability
- point mutations
- translocations
- gene amplification
Identifying oncogenes through tumor viruses
Retroviral genome integrates to host genome and activate a proto-oncogene
Genes near viral integration sites in cancer cells may be oncogenes
Ras oncogene
Normal ras is inactive until binding of growth factors to receptors
Oncogenic ras is constitutively active
Genetic predisposition to cancer
Retinoblastoma caused by mutations in RB gene, individuals who inherit RB- allele are prone to cancer of retina, due to proliferation of retinal cells, RB+ tumors develop due to RB-/RB+ cells
Chemotherapy
drugs may kill cancer cells unreachable by surgery
- directed against cell proliferation pathways
- normal proliferating cells killed by chemotherapy
