Oncogenes

In 1911 Peyton Rous reported that a class of RNA viruses can cause tumors in animals. These RNA tumor viruses, called "retroviruses," carry an RNA genome that, once inside a cell, is copied into DNA, which then is inserted randomly into the genome of a host cell. Some retroviruses are slow to cause tumors. After infection and spread to a large number of cells, a DNA copy of the viral genome, by chance, integrates into a host cell's DNA next to a normal gene that plays an important role in cell growth. If this viral integration disrupts the expression or structure of the normal cellular gene, it induces abnormal growth signals that can lead to cancer.

Other retroviruses cause tumors to appear very quickly. In the process of copying viral RNA into DNA, RNA that is expressed from cellular genes can be mistakenly copied into the viral genome. The progeny of the virus transfer the cellular gene to many other cells. If this "captured" cellular RNA is from a gene that stimulates cell growth, it then causes abnormal growth stimulation, leading to cancer. This process is termed "gene capture."

Through molecular cloning, the genes that are activated or captured by retroviruses have been identified and characterized. Almost three dozen such retroviral oncogenes and their related cellular proto-oncogenes are now known.

Oncogenes and tumor suppressor genes collaborate to "short circuit" normal growth regulatory pathways in cells. A generic growth-signaling pathway is shown where a growth factor binds to its receptor, which stimulates a cascade of signals inside the cell. The signals culminate in the nucleus, where they induce expression of genes involved in stimulating cell proliferation. On the left side are different steps in the signaling pathway that can be affected by activation of oncogenes. On the right side are growth inhibitory steps that can be lost by inactivation of tumor suppressor genes. In parentheses are examples of oncogenes and tumor suppressor genes that are mentioned in the text.