Many cells normally undergo an apoptosis program. In the presence of an activated oncogene, disorderly survival and proliferation can be observed. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many new cancer drugs target those DNA sequences and their products.
Mutations in microRNAs can lead to activation of oncogenes. New research indicates that small RNAs 21-25 nucleotides in length called microRNAs (miRNAs) can control expression of these genes by downregulating them.
|Growth factors, or mitogens||c-Sis||Usually secreted by specialized cells to induce cell proliferation in themselves, nearby cells, or distant cells. An oncogene may cause a cell to secrete growth factors even though it does not normally do so. It will thereby induce its own uncontrolled proliferation (autocrine loop), and proliferation of neighboring cells. It may also cause production of growth hormones in other parts of the body.|
|Receptor tyrosine kinases||epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR), HER2/neu||Kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receive protein signals from outside the cell and transmit them to the inside of the cell). Tyrosine kinases add phosphate groups to the amino acid tyrosine in the target protein. They can cause cancer by turning the receptor permanently on (constitutively), even without signals from outside the cell.|
|Cytoplasmic tyrosine kinases||Src-family, Syk-ZAP-70 family, and BTK family of tyrosine kinases, the Abl gene in CML - Philadelphia chromosome||-|
|Cytoplasmic Serine/threonine kinases and their regulatory subunits||Raf kinase, and cyclin-dependent kinases (through overexpression).||-|
|Regulatory GTPases||Ras protein||-|
|Transcription factors||myc gene||-|
Quantitative: Tumor formation is induced by an increase in the absolute number of proto-oncogene products or by its production in inappropriate cell types.
Qualitative: Conversion from proto-oncogene to transforming gene (c-onc) with changes in the nucleotide sequence which responsible for the acquisition of the new properties.
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.