Scientists at Emory University have discovered a new family of enzymes that appears to play a powerful role in generating the abnormal cell growth that occurs in both cancer and in some forms of cardiovascular disease. The enzymes appear to convert oxygen into a class of molecules known as "reactive oxygen", which has long been implicated in causing damage to cellular molecules such as DNA and in the aging process. The research is reported in the Sept. 2, 1999 issue of Nature.
Through their experiments with Mox1, one of the enzymes in the new class, the Emory scientists, led by biochemist J. David Lambeth, M.D., Ph.D., in collaboration with cardiology researcher Kathy Griendling, Ph.D., found that the reactive oxygen produced by the enzymes functions as a potent growth signal inside cells, instructing cells to divide more rapidly. Abnormal cell division or growth is seen in cancerous cells as well as in some forms of cardiovascular disease.
In the case of cancer, rapid and uncontrolled cell division leads to tumor formation. In cardiovascular disease, abnormal cell growth leads to the formation of plaques seen in hardening of the arteries (atherosclerosis) and in thickening of the blood vessel walls, which causes high blood pressure. Although scientists know that different molecular signals instruct cells to behave in various ways, the cellular mechanisms regulating cell growth have been poorly understood.
Dr. Lambeth and his colleagues first cloned the human Mox1 gene based on its similarity to an enzyme that generates reactive oxygen in neutrophils as a mechanism to kill bacteria. They then introduced the Mox1DNA into mouse cells and were surprised to observe that the cells took on the appearance of cancer cells and divided more rapidly than normal cells. When they injected these transformed cells into mice they found that the cells were extremely powerful in producing tumors.