Oncogenes 1976 – Understanding the Development of Cancer

Cell division depends on a specific sequence of events involving the proper processing of information in our genes. When this process goes wrong, uncontrolled cell growth or cancer may occur. Two general mechanisms facilitate a cell's progression toward cancer. The first involves proto-oncogenes, whose normal activity supports healthy cell proliferation. A proto-oncogene, in an altered form that may result from a mutation in its genetic sequence, becomes an oncogene that promotes excessive cell growth. Mutations may be triggered by radiation, chemicals or other means.

Tumor-suppressor (TS) genes, on the other hand, block events that lead to cancer. For example, some useful TS gene products can cause abnormal cells to undergo apoptosis (a normal and beneficial process of cell death). In a car analogy, oncogenes are accelerators pressed to the floor, while TS genes are the brakes. If either the accelerator or the brakes fail, the car can run wildly out of control.

In 1976, the American biologists J. Michael Bishop and Harold E. Varmus showed that oncogenes are defective proto-oncogenes found in many organisms, including humans. Bishop compared proto-oncogenes to material on which cancer-causing agents can act— “keyboards on which various carcinogens can play”.

Cancer-causing genes were first discovered in viruses and were shown to be copies of normal cellular genes. In short, viral oncogenes were proto-oncogenes incorporated into viruses in slightly altered form. When a virus invades a host cell and adds viral oncogenic genes, these can dangerously increase existing proto-oncogene activity. Cancers caused by these oncoviruses can sometimes be prevented with vaccines against the virus, and some oncogenic proteins in cancer cells can be targeted by monoclonal antibodies. In addition, oncogene expression can sometimes be suppressed by small RNA molecules called microRNAs. Conversely, mutations in such microRNAs (oncomirs) can activate oncogenes.

About the Article Image: A molecular model of the tumor-suppressor protein p53 bound to a strand of DNA. Mutations that inactivate this protein, normally the “guardian of the genome,” can cause cancers. While oncogenes act like an accelerator, p53 acts like a brake.

Historical Figures Mentioned in the Article: John Michael Bishop (b. 1936), Harold Elliot Varmus (b. 1939)

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