| In unicellular organisms such as bacteria, natural selection favors those cells that are most efficient at growing and dividing and, generally, proliferation is simply limited by the availability of nutrients. In contrast, in multicellular organisms such as human beings, there are elaborate controls on the proliferation of individual cell types to maintain the overall integrity of the organism both in terms of the number of individual cell types and also with respect to their spatial organization. Indeed, in adults, despite a plentiful supply of nutrients, the vast majority of cells are not dividing; furthermore, deregulation of growth control leads to the development of tumors and cancer. However, under certain conditions such as tissue repair and senescence, regulated growth and proliferation is promoted. Thus, as cells die, either by senescence or as a result of tissue damage, they must be replaced in a strictly regulated manner.
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| Cellular homeostasis maintains organ integrity through controlled cell survival, proliferation and cell death (by apoptosis) to ensure that normal cells, unlike cancerous (transformed) cells, generally stop dividing when they contact neighboring cells.
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| Much of what we now know about the control of normal cell growth and division has arisen from cancer research; analysis of the genetic alterations in cancer cells has revealed mutations in a large number of genes involved in the control of normal cell proliferation. These genes can be classified as proliferative or antiproliferative.
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| Mutated proliferative genes are called oncogenes (cancer-causing genes), the normal cellular counterparts of which are called proto-oncogenes
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| Proto-oncogenes are predominantly signal transducers that act to promote normal cell growth and division; aberrant regulation of these processes leads to cellular transformation.
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| In contrast, the antiproliferative genes or tumor suppressor genes normally act to suppress cell proliferation
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| Mutations that inactivate or lead to loss of expression of tumor suppressor genes therefore also lead to uncontrolled proliferation. Thus, whereas the mutant phenotype of tumor suppressor genes is usually recessive and generally requires loss or inactivation of both alleles for its expression, a mutation in only one allele of a proto-oncogene is required to bring about cell transformation (dominant mutant phenotype).
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