The deregulation of the balance between proliferation and programmed cell death is considered one of the most important features of malignant tumors. The search for new markers, which may reflect the tumor progress and response to various therapy regimens, has recently focused on alterations of genes involved in regulation of programmed cell death and apoptosis. Thebcl-2-family is a still growing family of genes, which play a major role in regulation of cell suicide, acting either as inhibitors (e.g.,bcl-2, bcl-xl, mcl-1) or promoters (e.g.,bcl-xs, bax, bak, bad)of apoptosis (1 -3 ). The chromosomal translocation t(14;18), leading to overexpression of theBcl-2protein was first described in human B-cell lymphoma (4 ). Later on, Bcl-2-overexpression without chromosomal translocations was also detected in various epithelial tumors (5 -12 ). It has been suggested thatBcl-2as the major inhibitor of apoptosis plays a role in tumor development and progress by prolonging the survival of malignant cells. Unexpectedly, expressionof Bcl-2has been shown to be connected with parameters of favorable prognosis and prolonged survival in nonsmall-cell lung cancer (6 ), breast (7 -9 ), and, recently, in ovarian cancer (10 -12 ). Bax-expression, in contrast, was associated with an unfavorable outcome, as well as negative histopathological features in breast (13 ) and ovarian cancer (12 ). Moreover, the association ofBax-expression with predictors of poor clinical outcome was strongly connected with concomitant downregulation ofBcl-2-expression (12 ,13 ). The unexpected effectof Bcl-2- and Bax-expression on prognosis of ovarian cancer patients is underlined by the survival curves of patients. Especially, patients with exclusivelyBax-positive tumors had a statistically significantly reduced survival as compared to patients with exclusivelyBcl-2-positive tumors (12 ). This difference could be observed for patients with tumors of different stage and grade, as well as for patients with no evidence of disease or residual tumor after primary surgery (12 ). One explanation for these observations is that the apoptosis inhibiting or promoting effect of these homologous proteins depends partly on protein-protein interactions.Bax,for example, the main antagonist ofBcl-2,heterodimerizes withBcl-2orBcl-Xland homodimerizes with itself (1 -3 ). The ratio of Bax-heterodimers to Bax-homodimers seems to be the critical determinant for regulating cell death (2 ,3 ). In cells in which 80% ofBaxis found in homodimers, an apoptotic signal results in cell death (2 ,3 ), suggesting a crucial role of theBax/Bcl-2balance for the regulation of proliferation or cell suicide.
