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An oncogene is a modified gene, or a set of nucleotides that codes for a protein, that increases the malignancy of a tumor cell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal cell develops into a tumor cell, possibly resulting in cancer. New research indicates that small RNAs 21-25 nucleotides in length called miRNAs can control expression of these genes by downregulating them. The first oncogene was discovered in 1970 and was termed SRC (pronounced SARK). Src was in fact first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr G. Steve Martin of the University of California, Berkeley demonstrated that the SRC was indeed the oncogene of the virus. In 1976 Drs. J. Michael Bishop and Harold E. Varmus of the University of California, San Francisco demonstrated that oncogenes were defective proto-oncogenes, found in many organisms including humans. For this discovery Bishop and Varmus were awarded the Nobel Prize in 1989.
Proto-oncogene A proto-oncogene is a normal gene that can become an oncogene, either after mutation or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through its protein product. Upon activation, it (or its product) becomes a tumor inducing agent, an oncogene. Activation The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types: Growth factors Growth factors, or mitogens, are usually secreted by a few specialized cells to induce cell proliferation in paracrine, autocrine, or endocrine manner. If a cell that usually does not produce growth factors suddenly starts to do so (because it developed an oncogene), it will thereby induce its own uncontrolled proliferation (autocrine loop), as well as the proliferation of neighboring cells. In addition, abnormal growth of endocrine glands often cause ectopic production of growth hormones that have secondary effects on other parts of the body. Protein kinases and related proteins There are six known classes of protein kinases and related proteins that can become an oncogene: See also | ||||||||
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