tumor suppressor gene

tumor suppressor gene, any of a class of genes that are normally involved in regulating cell growth but that may become cancer-causing when damaged. Tumor suppressor genes encode for proteins that are involved in inhibiting the proliferation of cells, which is crucial to normal cell development and differentiation. Because of this ability, tumor suppressor genes can also act to stem the uncontrolled growth of cancer cells. Genetic damage, or mutation, that occurs to these genes contributes to the development of a cancerous tumor.

Cancer research has led to the identification and characterization of many tumor suppressor genes. In 1971 American researcher Alfred Knudson, Jr., postulated that a rare form of eye cancer called retinoblastoma is caused by mutations in a gene designated RB. Subsequent research revealed that mutations in this gene also play a role in cancers of the bone, lung, breast, cervix, prostate, and bladder. A number of other tumor suppressor genes (such as TP53, which encodes a protein known as p53) have been identified. The mutated form of TP53 has been implicated in more than 50 percent of all cancers. Mutations in two other tumor suppressor genes, BRCA1 and BRCA2, are associated with an increased susceptiblity to breast cancer; they are found in 5 to 10 percent of all cases and in about 85 percent of all cases of inherited breast cancer.

The tumor suppressor genes in a healthy cell work together with another class of genes, called proto-oncogenes, to control cell reproduction. tumor suppressor genes code for proteins that restrain cell growth, and proto-oncogenes specify proteins that stimulate cell growth. Mutations in either type of gene can disrupt the delicate balance between inhibition and activation of the molecular processes that regulate a cell’s life cycle, leading to the uncontrolled cell growth characteristic of cancer. A mutation in one gene alone does not cause a malignant tumor to develop; a number of genetic insults occurring in a few different genes over time are necessary for a cell to undergo transformation to a malignant state. For example, a proto-oncogene becomes a cancer-causing oncogene when mutated in a manner that increases the cell’s propensity to divide excessively. In order for a cell to give rise to cancer, other mutations, such as damage to a tumor suppressor gene, must arise.

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Usually many decades are required for mutations leading to cancer to be accumulated. Cases do occur, however, in younger individuals, many of which are believed to result from a mutation passed from parent to child. Some forms of cancer are associated with an inherited mutation in a tumor suppressor gene. One such familial syndrome, called familial adenomatous polyposis, is a condition in which tumors of the colon arise due to an inherited mutation in the tumor suppressor gene APC.