|MoBio||Genes and Cancer||Chapter 10|
Genes and Cancer
Chemicals (e.g., from smoking), radiation, viruses, and heredity all contribute to the development of cancer by triggering changes in a cell's genes. Chemicals and radiation act by damaging genes, viruses introduce their own genes into cells, and heredity passes on alterations in genes that make a person more susceptible to cancer. Genes are inherited instructions that reside within a person's chromosomes. Each gene instructs a cell how to build a specific product--in most cases, a particular kind of protein. Genes are altered, or "mutated," in various ways as part of the mechanism by which cancer arises.
One group of genes implicated in the development of cancer are damaged genes, called "oncogenes." Oncogenes are genes whose PRESENCE in certain forms and/or overactivity can stimulate the development of cancer. When oncogenes arise in normal cells, they can contribute to the development of cancer by instructing cells to make proteins that stimulate excessive cell growth and division.
Proto-Oncogenes and Normal Cell Growth
Oncogenes are related to normal genes called proto-oncogenes that encode components of the cell's normal growth-control pathway. Some of these components are growth factors, receptors, signaling enzymes, and transcription factors. Growth factors bind to receptors on the cell surface, which activate signaling enzymes inside the cell that, in turn, activate special proteins called transcription factors inside the cell's nucleus. The activated transcription factors "turn on" the genes required for cell growth and proliferation.
Oncogenes are Mutant Forms of Proto-Oncogenes
Oncogenes arise from the mutation of proto-oncogenes. They resemble proto-oncogenes in that they code for the production of proteins involved in growth control. However, oncogenes code for an altered version (or excessive quantities) of these growth-control proteins, thereby disrupting a cell's growth-signaling pathway.
By producing abnormal versions or quantities of cellular growth-control proteins, oncogenes cause a cell's growth-signaling pathway to become hyperactive. To use a simple metaphor, the growth-control pathway is like the gas pedal of an automobile. The more active the pathway, the faster cells grow and divide. The presence of an oncogene is like having a gas pedal that is stuck to the floorboard, causing the cell to continually grow and divide. A cancer cell may contain one or more oncogenes, which means that one or more components in this pathway will be abnormal.
Tumor Suppressor Genes
A second group of genes implicated in cancer are the "tumor suppressor genes." Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer. In other words, if a pair of tumor suppressor genes are either lost from a cell or inactivated by mutation, their functional absence might allow cancer to develop. Individuals who inherit an increased risk of developing cancer often are born with one defective copy of a tumor suppressor gene. Because genes come in pairs (one inherited from each parent), an inherited defect in one copy will not lead to cancer because the other normal copy is still functional. But if the second copy undergoes mutation, the person then may develop cancer because there no longer is any functional copy of the gene.
Tumor Suppressor Genes Act Like a Brake Pedal
Tumor suppressor genes are a family of normal genes that instruct cells to produce proteins that restrain cell growth and division. Since tumor suppressor genes code for proteins that slow down cell growth and division, the loss of such proteins allows a cell to grow and divide in an uncontrolled fashion. Tumor suppressor genes are like the brake pedal of an automobile. The loss of a tumor suppressor gene function is like having a brake pedal that does not function properly, thereby allowing the cell to grow and divide continually.
p53 Tumor Suppressor Protein Triggers Cell Suicide
One particular tumor suppressor gene codes for a protein called "p53" that can trigger cell suicide (apoptosis). In cells that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division. If the damage cannot be repaired, the p53 protein eventually initiates cell suicide, thereby preventing the genetically damaged cell from growing out of control.
[This page was adapted from National Cancer Institute.]