Oncogenes and cancer suppressor genes

Cancer is caused by the malfunction of genes that regulate cell proliferation. Two kinds of regulatory genes have been discovered in the search for cancer genes: those that promote growth, called oncogenes, and those that suppress growth, called anti-oncogenes or cancer suppressor genes. The retroviruses that cause animal cancers contain oncogenes coding for growth-promoting signals. These retroviruses rarely cause human cancer but study of their oncogenes has allowed identification of many human cancer genes. These genes code for growth factors, growth factor receptors, cytoplasmic proteins, and nuclear proteins. The complete sequence of cellular growth control begins when a growth factor binds to its receptor and acts directly or indirectly through a G protein and second messenger to induce phosphorylation (activation) of an intracellular protein that ultimately alters the expression of the genes necessary to initiate cell division. At each step in the complex sequence that up-regulates cell division, there is an opposite down-regulating activity produced by the protein products of anti-oncogenes or cancer suppressor genes. These proteins do this by binding to and inactivating transcription factors that initiate DNA synthesis or by directly inactivating the molecules activated by the oncogene products. When this carefully orchestrated and regulated cell control process goes awry because one or more of the proteins in the sequence has been altered by a mutated gene, the cell divides in an uncontrolled manner and malignancy results. It is thought that most human cancers result from a combination of genetic changes that must include both the absence of the protein products of cancer suppressor genes and the presence of abnormal products of oncogenes. The work of Volgelstein and coworkers at Johns Hopkins University has provided the best insight so far into the complex pathogenesis of a common tumor, colon cancer. Carcinogenesis in colon cancer requires a sequence of events that involves more than five genes. Understanding of these pathogenic mechanisms should improve cancer diagnosis and treatment.