Molecular Basis For Cancer Flashcards
Theory of colonial evolution of cancer
. Initial damage/mutation occurs in single cell that allows cells to grow w/ selective growth advantage
. Eventually outgrows neighbor cells
. In colonial population, a single cell may acquire 2nd mutation providing additional growth advantage and allowing it to expand and become predominant cell
. Repeated cycles colonial expansion lead to fully developed malignant tumor
Hallmarks of cancer
. Self-sufficiency of growth signals . Insensitivity to growth inhibitory signals . Evasion of apoptosis . Limitless replication potential . Sustained angiogenesis
Self-sufficiency of growth signals in cancer cells
. Mutation in GFs that transmit growth signals from 1 cell to another
. Mutation in GF receptors on cell surface
. Mutation in signal tansduction molecules that activate cascade of phosphorylation rxns w/in cell
. Mutation in nuclear TFs
. Allows cell proliferation despite having an inactive growth receptor
Porto-oncogenes
. Genes whose protein products control cell growth and differentiation
. When they undergo mutations causing qualitative and quantitative changes in gene products they become oncogenes
Oncogenes
. Genes whose expression results in neoplasticism transformation
. Normally from Porto-oncogenes, but can be from mutations that lead to structural changes or inc. expression
. Dominant
Tumor suppressor genes in formation of cancer
. Normally inhibit growth
. Loss of gene function from mutations lead to cell transformation by removing restraints that normally regulate growth
. Retinoblastoma tumor suppressor, p53, BRCA1 and 2 are examples
. Recessive
P53 functions
. Regulator fo gene expression and control genes in growth regulation
. Role in DNA repair through G1 arrest until damage is repaired
. Controls apoptosis by triggering it if cell damage is beyond repair
How does a cell get limitless replication potential?
. Reappearance of enzyme telomerase
P53 role in angiogenesis
. Directed synthesis of anti-angiogenic factor thrombospondin to restrict ability of cells to induce angiogenesis
. When p53 mutates, antiangiogenic factor is no longer made and angiogenesis cans occur
Proliferative cells metabolize glucose primarily through ____
. Glycolysis
. Excrete a large amt of carbon in form of lactate or other metabolic acid
T/F cell won’t uptake nutrients unless stimulated by growth factors
T, cancer cells overcome this through genetic mutations that alter receptors so here is constitutive uptake and metabolism of nutrients
Warburg effect
. In presence of O2 most differentiated cells metabolize glucose to CO2 via oxidative phosphorylation
. Most cancer cells produce large amount of lactate regardless of availability of O2 (aerobic glycolysis)
Why do proliferating cells switch to less efficient metabolism?
. For cells to proliferate the bulk of glucose can’t be committed to catabolism for just ATP production, if it was ATP ratio would be too high impairing flux of glycolytic intermediates limiting acetyl CoA and NADPH required for macromolecule synthesis
. Glycolytic oxidation provides energy and raw materials required for production of new cells
Normal resting cells use ___ to satisfy requirements cells
. Catabolic metabolism
. Met through fatty acid oxidation and oxidative metabolism of glucose
Upon growth factor stimulation, proliferation cells inc. uptake of ____
Glucose and glutamine
