Protooncogene

An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated and/or expressed at high levels.

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. Most oncogenes began as proto-oncogenes, normal genes involved in cell growth and proliferation or inhibition of apoptosis. If normal genes promoting cellular growth, through mutation, are up-regulated, (gain of function mutation) they will predispose the cell to cancer and are thus termed oncogenes. Usually multiple oncogenes, along with mutated apoptotic and/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.

The theory of oncogenes was foreshadowed by the German biologist Theodor Boveri in his 1914 book Zur Frage der Entstehung Maligner Tumoren ('The Origin of Malignant Tumours'), Gustav Fisher, Jena, 1914. Oncogenes (Teilungsfoerdernde Chromosomen) that become amplified (im permanenten Übergewicht) during tumour development.

Later on the term "oncogene" was rediscovered in 1969 by National Cancer Institute scientists George Todaro and Robert Heubner.

The first confirmed oncogene was discovered in 1970 and was termed src (pronounced sarc as in sarcoma). 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. The first nucleotide sequence of v-src was sequenced in 1980 by A.P. Czernilofsky et al.

In 1976 Drs. Dominique Stehelin, J. Michael Bishop and Harold E. Varmus of the University of California, San Francisco demonstrated that oncogenes were activated proto-oncogenes, found in many organisms including humans. For this discovery, proving Todaro and Heubner's "oncogene theory", Bishop and Varmus were awarded the Nobel Prize in Physiology or Medicine in 1989.

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