The genes that normally regulate cell growth and division during the cell cycle include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways. Mutations that alter any of these genes in somatic cells can lead to cancer. The agent of such change can be random spontaneous mutation. However, it is also likely that many cancer-causing mutations result from environmental influences, such as chemical carcinogens, X-rays and other high-energy radiation, and some viruses.
Cancer research led to the discovery of cancer-causing genes called oncogenes (from the Greek onco, tumor) in certain types of viruses. Subsequently, close counterparts of viral oncogenes were found in the genomes of humans and other animals. The normal versions of the cellular genes, called proto-oncogenes, code for proteins that stimulate normal cell growth and division.
How might a proto-oncogene—a gene that has an essential function in normal cells—become an oncogene, a cancer causing gene? In general, an oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogene’s protein product or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes fall into three main categories: movement of DNA within the genome, amplification of a proto-oncogene, and point mutations in a control element or in the proto-oncogene itself.
Cancer cells are frequently found to contain chromosomes that have broken and rejoined incorrectly, trans-locating fragments from one chromosome to another. Having learned how gene expression is regulated, you can now see the possible consequences of such trans-locations. If a trans-located proto-oncogene ends up near an especially active promoter (or other control element), its transcription may increase, making it an oncogene. The second main type of genetic change, amplification, increases the number of copies of the proto-oncogene in the cell through repeated gene duplication. The third possibility is a point mutation either in the promoter or an enhancer that controls a proto-oncogene, causing an increase in its expression, or in the coding sequence of the proto-oncogene, changing the gene’s product to a protein that is more active or more resistant to degradation than the normal protein. These mechanisms can lead to abnormal stimulation of the cell cycle and put the cell on the path to becoming a cancer cell.
In addition to genes whose products normally promote cell division, cells contain genes whose normal products inhibit cell division. Such genes are called tumor-suppressor genes since the proteins they encode help prevent uncontrolled cell growth. Any mutation that decreases the normal activity of a tumor-suppressor protein may contribute to the onset of cancer, in effect stimulating growth through the absence of suppression.
The protein products of tumor-suppressor genes have various functions. Some repair damaged DNA, a function that prevents the cell from accumulating cancer-causing mutations. Other tumor-suppressor proteins control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissues—and is often absent in cancers. Still other tumor-suppressor proteins are components of cell signaling pathways that inhibit the cell cycle.
Urry, Lisa A.. Campbell Biology (p. 386). Pearson Education. Kindle Edition.