Research Helps Shed Light on Role of Apoptosis in Tumor Development and Growth

OncologyONCOLOGY Vol 11 No 8
Volume 11
Issue 8

Many types of cells undergo apoptosis as part of the normal physiological process. An interruption in apoptosis is thought to be a primary cause of tumor growth. Two presentations concerning this subject were made at the 88th Annual Meeting of the

Many types of cells undergo apoptosis as part of the normal physiologicalprocess. An interruption in apoptosis is thought to be a primary causeof tumor growth. Two presentations concerning this subject were made atthe 88th Annual Meeting of the American Association for Cancer Research(AACR).

In the first presentation, Stanley J. Korsmeyer, MD, of the Howard HughesMedical Institute at Washington University School of Medicine in St. Louis,discussed a series of genes, B-cell lymphoma 2 (bcl-2), bax,bad, and abid, that regulate cell death. The bcl-2 proteinhas the novel function of blocking programmed cell death, extending thesurvival of cells normally destined to die. For example, mice that over-expressbcl-2 progress to life-threatening lymphoma. According to Korsmeyer,bcl-2 does not act alone but duels with its counteracting twin,bax. When bax is in excess, cells execute the programed death command.However, when bcl-2 dominates, the process is interrupted and cellssurvive.

In studies of bcl-2-deficient mice, Dr. Korsmeyer found thatthe embryos developed normally. However, when the mice reached adulthood,bax predominated, leading to massive cell death of lymphocytes andthe disappearance of lymphoid organs. In addition, the embryonic loss ofkidney cells led to polycystic kidney disease, and the death of melanocytescaused hair hypopigmentation. When Dr. Korsmeyer studied bax-deficientmice, he found that bcl-2 predominated. These mice displayed cellularhyperplasia and aberrations in cell death during the development of thetestes.

According to Dr. Korsmeyer, "bcl-2 represents an importantcontrol step in the common pathway of apoptosis present in all cells. Evidenceindicating that it serves as a critical checkpoint includes its role inthe generation of human disease, its importance in developmental cell death,and its selection as a site of interference by DNA viruses. Further studyof the bcl-2 family holds the promise of improving our understandingof the pathway of programmed cell death and the aberrations in this processthat result in malignancy."

A Second Study

In another study, Huachen Wei, MD, PhD, Associate Professor of Dermatologyat the Mount Sinai School of Medicine in New York, and his colleagues evaluatedmethods of regulating apoptosis as a new approach to the understandingof ultraviolet-induced carcinogenesis. They hypothesized that apoptosiscould be induced by stimulating the tumor suppressor gene p53 orby down-regulating the expression of the apoptosis suppressor gene bcl-2.The p53 gene is thought to suppress tumor growth through two mechanisms:by arresting cell growth at a specific phase in the cell cycle and by inducingapoptosis. Mutations in this gene are thought to be the most common geneticmutations in human cancers.

Using a cell line that expresses both p53 and bcl-2, theinvestigators found that ultraviolet B radiation (UVB) significantly inducedthe expression of p53 in a dose- and time-dependent manner. However,exposure to the equally cytotoxic dose of ultraviolet A radiation (UVA)produced no effects on p53 expression. On the other hand, UVA substantiallydown-regulated the expression of bcl-2, whereas exposure to thesame level of UVB produced no change in the expression of bcl-2.

"Our results indicate that both UVA and UVB cause cell damage andinduce apoptosis by completely separate mechanisms," said Dr. Wei."Because mutations in p53 and over-expression of bcl-2can result in human cancers, our findings suggest that ultraviolet radiationmay provide a new approach for drug development," said Dr. Wei.

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