What are Oncogenes?

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

Several different systems have been devised to classify oncogenes. Some of the different categories of oncogenes include:

• Growth factors or mitogens – These oncogenes stimulate the growth, proliferation, and differentiation of cells. Growth factors are usually steroids or proteins secreted by cells to stimulate their own cell proliferation or the proliferation of other nearby or distant cells. These oncogenes can stimulate the cell to secrete growth factors when it would not normally do so, thereby inducing the cell’s abnormal proliferation. An example of an oncogene in this class is c-Sis.
• Receptor tyrosine kinases – Examples of oncogenes in this class include the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and human epidermal growth factor receptor 2 (HER2/neu). The proteins encoded by these oncogenes are very important anti-cancer treatment targets.

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These kinases act by adding phosphate groups to other proteins to switch them on or off. The receptor kinases add phosphate groups to cell surface receptor proteins that transmit protein signals from the outside to the inside of the cell. Tyrosine kinases add these phosphate groups to tyrosine in the target proteins. This can cause cancer because the receptor is turned on continuously, even in the absence of extracellular signals.

• Cytoplasmic tyrosine kinases – Examples of these oncogenes include the Abl gene in chronic myeloid leukemia (the Philadelphia chromosome) and the Src family, Syk-ZAP-70 family, and BTK family of tyrosine kinases.
• Cytoplasmic serine/threonine kinases – Examples include Raf kinase and cyclin-dependent kinases.
• Regulatory GTPases – An example of a regulatory GTPase is the Ras protein that hydrolyses GTP into GDP and a phosphate. Once activated by a growth factor such as EGF or TGF beta, Ras acts as an on/off switch in major signaling pathways that lead to cellular growth and proliferation.
• Transcription factors – An example is the myc gene, which regulates the transcription of genes that induce cellular proliferation.

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