Carcinogenesis Flashcards
Name a well-known tumor suppressor gene.
BRCA1
What are mitogens?
They are growth factors that lead to changes in gene expression, ultimately resulting in cell cycle progression and proliferation
What is a pro-oncogene?
It is a non-mutated oncogene
Name some common oncogenes.
EGFR, K-ras, AKT, MAP kinase, c-myc, Bcl-2
Describe the function of tumor suppressor genes.
Think of them as the “brakes” on a car. They block tumor development by regulating the progression of cells through checkpoints in the cell cycle and by promoting programmed cell death to control division and survival
What is loss of heterozygosity?
Both copies of tumor suppressor genes require inactivating mutations, and one a germline mutation and both alleles become mutated, there is LOH facilitating tumor formation
Discuss dominant versus recessive mutations and their relationship with mutated oncogenes and tumor suppressor genes.
Oncogene mutations are dominant so only one allele is needed to abnormally activate the oncogene. Tumor suppressor gene mutations are recessive so both alleles must be mutated to inactivate their normal fxn
Name the major categories of genotoxic carcinogens.
Organic- polycyclic aromatic hydrocarbons and mycotoxins.
Physical- radiation, asbestos, heavy metals
Discuss benzene exposure and its potential consequences.
Occupational exposure from solvents, 100% alcohol, tobacco smoke, and crude oil/gasoline. Acute toxicity causes CNS depression, arrhythmias, and chemical pna. Chronic toxicity is hematotoxic and can cause leukemia
What is the initiation phase of carcinogenesis?
It is mutagenic (unrepaired DNA) and thus irreversible. It occurs in an individual cell (clone)
Describe the function of oncogenes.
They facilitate cell cycle progression, like a gas pedal on a car and when they are mutated, the pedal can’t be release and is always “on”. They encode proteins in signaling pathways, transcription factors for growth-promoting genes, and inhibitors of apoptosis.
What is the promotion phase of carcinogenesis?
It is non-mutagenic and reversible (e.g. stop exposure) and promotes cell proliferation
