cancer

• Hyperplasia: cell division rate is still disordered
• Mild dysplasia: changes in morphology
• A single mutation is not enough, cancer cells must accumulate a number of somatic mutations over time that are inherited by daughter cells
• Clonal expansion increases the number of abnormal daughter cells able to acquire further mutation
• There is progressive neoplastic transformations of daughter cells as more genetic mutations are acquired
• 6 mutations are required to be a cancer
• extrinsic causes of mutations: chemicals, infectious agents, radiation
• intrinsic causes of mutations: dna replication errors or failure to repair DNA
• Proto-oncogenes encode proteins involved in normal cell proliferation: growth factors, receptors for growth factors, intracellular signalling proteins, gene regulatory proteins
• Oncogenes are mutant overactive or overexpressed proto-oncogenes that produce abnormal, increased cell proliferation
• Overactivity (gain of function): needs a mutation of one allele sufficient to see an effect
• point mutation in Ras (encodes an intracellular signalling protein in a pathway that promotes proliferation), in cancer Ras remains in the active GTP bound form and stimulates proliferation even when growth factor is absent
• Loss of Rb leads to loss of cell cycle control and increased cell proliferatio
• Underactivity mutation: both alleles must be mutated to see an effect
• Balanced rate of cell division and apoptosis leads to homeostasis, an increase in either will result in a tumour
• Familial cases: inheritance of a mutated allele (first hit) by all cells is not sufficient for cancer, second hit causes cancer, early onse
• Sporadic cases: both hits are acquired after both and must b in the same somatic cell to cause cancer, late onset
• Loss of e-cadherin (cell adhesion molecule) increases cell motility
• Angiogenesis: increased VEGF production induces blood vessel formation
• Telomerase enzyme maintains telomere length in stem cells; otherwise, its expression silenced