Regulation of apoptosis by oncogenes

✍ Scribed by Douglas R. Green; Anne McGahon; Seamus J. Martin

• Book ID: 102655813
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 644 KB
• Volume: 60
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960101)60:1<33::aid-jcb6>3.0.co;2-4

✦ Synopsis

Cancer is usually envisioned as a disease of cellular proliferation. That is, loss of controls on cell proliferation is viewed as being the central, underlying cause of cancer. Recently, however, this idea has undergone a change. With the realization that cell number is a result of the competing effects of cell proliferation and cell death, the latter has taken on a larger significance. Furthermore, like cell proliferation, cell death can be subject to molecular control. Thus, many recent studies suggest that cancer can result from loss of regulation of either cell proliferation or cell death, and here we argue that it is often a combination of the two.

Apoptosis, or active cell death, is thought to be of particular importance in this regard. The significance of apoptosis in the process of oncogenesis is underscored by at least three important observations. The first is that most physical and chemical agents with antitumor activity act to induce apoptosis, as do genes that potentiate their effects [l-31. The second is that the frequency of apoptotic cells in a tumor correlates very well with outcome. That is, tumors with low apoptotic indices tend to be more agressive than are those displaying higher incidence of apoptotic cell death, and thus apoptosis is almost certainly an important factor in the rate of tumor growth [41. By contrast, the frequency of necrotic cell death is inversely correlated with outcome (which might, at first glance, be counter-intuitive). The third observation is that a number of oncogenes and anti-oncogenes have been found to regulate the process of apoptosis [2,3,5]. Together, these observations make a strong case for studying apoptosis as a route to understanding oncogenesis.

Thus, the induction of apoptosis should be an important goal of cancer therapy. However, antiapoptotic activities exist within cells and these