DETECTION OF THE APOPTOSIS-SUPPRESSING ONCOPROTEIN BCL-2 IN HORMONE-REFRACTORY HUMAN PROSTATE CANCERS

The oncoprotein encoded by bc1-2 is unique because of its intracellula r location (a mitochondrial membrane protein) and apparent mode of act ion (suppression of apoptosis). To date, this oncogene has been associ ated only with the development of certain forms of human B-cell lympho ma. In this report, we describe our experience with a monoclonal antib ody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing t his proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to eva luate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the b asal cells. An epithelial cells in areas of prostatic intrepithelial n eoplasia were stained by this antibody, as were most (62%) localized i nvasive prostatic carcinomas. In contrast, all primary prostatic carci nomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1 -2 can be detected at sequential stages in the natural history of huma n prostate cancer. Since the bc1-2 oncoprotein is known to suppress th e cellular response to apoptotic stimuli, it will be important to dete rmine whether bc1-2 expression is a factor in the development of prost ate cancers and in the survival of hormone-refractory prostate cancer cells.