EXPRESSION OF THE APOPTOSIS-SUPPRESSING GENE BCL-2 IN PHEOCHROMOCYTOMA IS ASSOCIATED WITH THE EXPRESSION OF C-MYC

It has become increasingly clear that deregulation of programmed cell death is a critical component in multistep tumorigenesis. Previous stu dies have demonstrated a high frequency of Bcl-2 expression in tumors arising from cells derived from the neural crest and in tumor cell lin es of neural origin. The present investigation was undertaken to deter mine whether similar molecular events occur in human pheochromocytoma. With the aim of determining the potential role of apoptosis in the pa thogenesis of this tumor, we assessed proto-oncogene Bcl-2 and c-myc p rotein products as well as Bcl-2 messenger RNA levels in a collection of such tumors. Western blot analysis revealed that such tumors expres sed the 26 kDa Bcl-2 (5 of 8 cases) and the 64 kDa c-Myc (7 of 8 cases ) proteins. Northern blot analysis detected the Bcl-2 transcripts in 6 of 8 tumors. Immunoperoxidase staining, using a monoclonal anti-Bcl-2 antibody, was positive in 18 (82%), including 5 malignant tumors, of the 22 specimens examined. This Bcl-2 immunoreactivity was seen in 14 of 18 (78%) sporadic tumors, including 2 that were extra-adrenal, and all familial tumors. Of the 22 tumor samples examined for c-Myc protei n, 20 (91%) tumors were positive. Our results suggest that deregulatio n of programmed cell death may be a critical component in the multiste p tumorigenesis of human pheochromocytoma. The genetic complementation of simultaneously deregulated Bcl-2 and c-myc may be implicated in th is process.