Molecular Mechanisms of Cancer

Cancer involves uncontrolled cell division and tissue invasiveness (metastasis) caused by a series of mutations in the genes of proteins that regulate the cell cycle. These mutations typically involve either promotion of cell division or inactivation of cell cycle suppression. Proto-oncogenes are normal genes that promote cell growth and mitosis, whereas tumor suppressor genes repress cell growth. Proto-oncogenes can be mutated by carcinogens to become oncogenes that produce excessive levels of growth promoting proteins. Tumor suppressor gene products, typified by p53, are frequently transcription factors that suppress mitosis and cell growth to allow DNA repair. Nearly half of all cancers involve p53 mutations. Mutations in another tumor suppressor gene, BRCA1, are associated with more than 80% of inherited breast and ovarian cancers. Cancer results from cumulative mutations of proto-oncogenes and suppressor genes that together allow unregulated cell growth. Over time malignant cells can self-select for characteristics that make them more malignant by gaining the ability to avoid apoptosis; become immortalized due to over expression of telomerase; become growth-factor self-sufficient and resistant to anti-growth factors; increase cell division; alter differentiation; lose contact inhibition, leading to metastasis; and promote angiogenesis.