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Synonyms:bbl, bfy, bhy, FLJ92943, LFS1, MGC112612, P53, TP53, Trp53

Molecular Mechanisms of Cancer

Cancer (neoplasm) is a family of diseases that involve uncontrolled cell division and tissue invasiveness (metastasis). During metastasis, malignant cells travel among tissues via the circulatory and/or lymphatic system. Unregulated cell growth and metastasis are caused by mutations in the genes (DNA) of proteins involved in the regulation of the cell cycle. Agents that cause DNA damage leading to the transformation of a cell are called carcinogens. Cancers are categorized according to their cell-type of origin as carcinoma (epithelial cell); lymphoma and leukemia (blood and bone marrow cells); sarcoma (mesenchymal); mesothelioma (mesothelial cells that line the peritoneal and pleural cavities); glioma (glial brain cell), germinoma (germ cell of the ovary or testes) and choriocarcinoma (placenta).

Cancers result from a series (progression) of gene mutations that typically involve two categories of function: promotion of cell division and inactivation of cell cycle suppression. Proto-oncogenes are normal genes that promote cell growth and mitosis, whereas tumor suppressor genes discourage cell growth. Proto-oncogenes can be mutated by carcinogenic agents to become oncogenes. Oncogenes 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 for DNA repair. Nearly half of all cancers involve altered p53 genes. Other suppressor genes include Rb (retinoblastoma family), APC (adenomatous polyposis coli), SMAD4, TP53, p16/CDKN2A and BRCA (breast cancer susceptibility protein) types 1 and 2. Cancer results from cumulative mutations of proto-oncogenes and suppressor genes which together allow the unregulated growth of cells. Oncogenes are typically dominant because they provide gain-of-function, whereas suppressor genes are recessive. They contain loss-of function mutations. Both copies of a suppressor gene need to mutate to cause loss-of-suppressor function. Only one copy of a proto-oncogene needs to mutate for gain-of-function. Mutations of tumor suppressor genes can be inherited.

Over time malignant cells can self-select for characteristics that make them more malignant: ability to avoid apoptosis; immortalization due to over expression of telomerase; growth-factor self-sufficiency and resistance to anti-growth factors; increased cell division; altered differentiation; loss of contact inhibition, become metastatic; and able to promote angiogenesis.