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NIH ... Turning Discovery Into Health ®TOP Oncogene. The name of oncogene suggests it is a gene that can cause cancer. Initially, oncogenes were identified in viruses, which could cause cancers in animals. Later, it was found that oncogenes can be mutated copies of certain normal cellular genes also called proto-oncogenes. Intact proto-oncogenes play important functions, regulating normal cellular growth, division, and apoptosis, which is the name for programmed or controlled cell death. Oncogenes or mutated copies of the proto-oncogenes may lead to uncontrolled cell growth and the escape from cell death, which may result in cancer development. Illustration of how a normal cell is converted to a cancer cell, when an oncogene becomes activated An oncogene is a gene that has the potential to cause cancer.[1] In tumor cells, these genes are often mutated, or expressed at high levels.[2] Most normal cells will undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead.[3] Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predispose the cell to cancer; thus, they are termed "oncogenes". Usually multiple oncogenes, along with mutated apoptotic or tumor suppressor genes will all act in concert to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target the proteins encoded by oncogenes.[2][4][5][6] History[edit]The theory of oncogenes was foreshadowed by the German biologist Theodor Boveri in his 1914 book Zur Frage der Entstehung Maligner Tumoren (Concerning the Origin of Malignant Tumors) in which he predicted the existence of oncogenes (Teilungsfoerdernde Chromosomen) that become amplified (im permanenten Übergewicht) during tumor development.[7] Later on, the term "oncogene" was rediscovered in 1969 by National Cancer Institute scientists George Todaro and Robert Huebner.[8] The first confirmed oncogene was discovered in 1970 and was termed SRC (pronounced "sarc" as it is short for sarcoma). SRC was first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr. G. Steve Martin of the University of California, Berkeley demonstrated that SRC was indeed the gene of the virus that acted as an oncogene upon infection.[9] The first nucleotide sequence of v-Src was sequenced in 1980 by A.P. Czernilofsky et al.[10] In 1976, Drs. Dominique Stéhelin [fr], J. Michael Bishop and Harold E. Varmus of the University of California, San Francisco demonstrated that oncogenes were activated proto-oncogenes as is found in many organisms, including humans. Bishop and Varmus were awarded the Nobel Prize in Physiology or Medicine in 1989 for their discovery of the cellular origin of retroviral oncogenes.[11] Dr. Robert Weinberg is credited with discovering the first identified human oncogene in a human bladder cancer cell line.[12][13] The molecular nature of the mutation leading to oncogenesis was subsequently isolated and characterized by the Spanish biochemist Mariano Barbacid and published in Nature in 1982.[14] Dr. Barbacid spent the following months extending his research, eventually discovering that the oncogene was a mutated allele of HRAS and characterizing its activation mechanism. The resultant protein encoded by an oncogene is termed oncoprotein.[15] Oncogenes play an important role in the regulation or synthesis of proteins linked to tumorigenic cell growth. Some oncoproteins are accepted and used as tumor markers. Proto-oncogene[edit]A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate the cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon acquiring an activating mutation, a proto-oncogene becomes a tumor-inducing agent, an oncogene.[16] Examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK. The MYC gene is implicated in Burkitt's lymphoma, which starts when a chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene. The MYC gene codes for widely used transcription factors. When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates. Another example of an oncogene is the Bcr-Abl gene found on the Philadelphia chromosome, a piece of genetic material seen in Chronic Myelogenous Leukemia caused by the translocation of pieces from chromosomes 9 and 22. Bcr-Abl codes for a tyrosine kinase, which is constitutively active, leading to uncontrolled cell proliferation. (More information about the Philadelphia Chromosome below) Activation[edit]From proto-oncogene to oncogene The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:
The expression of oncogenes can be regulated by microRNAs (miRNAs), small RNAs 21-25 nucleotides in length that control gene expression by downregulating them.[18] Mutations in such microRNAs (known as oncomirs) can lead to activation of oncogenes.[19] Antisense messenger RNAs could theoretically be used to block the effects of oncogenes. Classification[edit]There are several systems for classifying oncogenes,[20] but there is not yet a widely accepted standard. They are sometimes grouped both spatially (moving from outside the cell inwards) and chronologically (parallelling the "normal" process of signal transduction). There are several categories that are commonly used:
Additional oncogenetic regulator properties include:
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What is a oncogene simple definition?(ON-koh-jeen) A mutated (changed) form of a type of gene called a proto-oncogene, which is involved in normal cell growth and division. When a proto-oncogene is changed so that too many copies are made or it becomes more active than normal, it is called an oncogene.
What is the function of a oncogene?Function of Oncogenes
They regulate cell proliferation, growth, and differentiation, as well as control of the cell cycle and apoptosis. The products of oncogenes include growth factors, growth factor receptors, signal transducers, transcription factors, and apoptosis regulators, as well as chromatin remodelers.
What are oncogenes examples?An example of an oncogene is the HER2 gene that makes HER2 protein. This protein helps control healthy breast cell division and growth. Extra copies of this gene may lead to an excess of HER2 protein, which causes cells to grow more quickly. The HER2 oncogene is found in some breast cancer and ovarian cancer cells.
Where are oncogenes?The ras oncogenes are not present in normal cells; rather, they are generated in tumor cells as a consequence of mutations that occur during tumor development.
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