Oncogenes

Normal cell growth is controlled by the availability of growth factors, which are hormone-like molecules that bind to specific receptors embedded in the surface membrane of cells. When this happens, the receptor stimulates a signaling cascade inside cells that ultimately tells the cells to divide. Many gene products in this signaling pathway are proto-oncogenes that can become oncogenes when activated by the different mechanisms described above. When a signaling proto-oncogene is activated, the signaling cascade becomes "short-circuited" and cells behave as if they are continually stimulated by their growth factor.

For example, the v-sis oncogene from a monkey cancer virus known as simian sarcoma retrovirus (SSV) comes from a gene that encodes platelet-derived growth factor, which stimulates growth of different cell types. Cells infected with SSV are, therefore, constantly bathed in the v-sis growth factor and stimulated to proliferate. Other oncogenes are mutated growth factor receptors where mutation leaves the receptor in the "on" status even in the absence of the growth factor. Two examples of mutated receptor onco-genes include v-erbB, found in a bird retrovirus that causes various cancers, and v-fms, which is carried by a mouse retrovirus that causes leukemia.

Inside the cell, components of the signaling cascade that connect cell surface growth receptors to the nucleus also can cause cancer when their activity is altered by mutation or overexpression. The Ras proto-oncogene is an example of a signal-transmitting molecule inside cells that can mutate into an oncogene. In the nucleus, these normal growth signals trigger other proteins, called transcription factors, that regulate gene expression needed for cell growth. Many transcription factors are proto-oncogenes. Two examples of proto-oncogene transcription factors are c-Fos and c-Jun, both of which were first identified as retroviral oncogenes.