Peptidylglycine alpha-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate

Most PCs show NE differentiation. Several studies have tried to correlate N E expression with disease status, but the reported findings have been contr adictory. Prostatic NE cells synthesize peptides with a wide spectrum of po tential functions. Some of these active peptides, such as PAMP, are amidate d. PAM is the only carboxy-terminal peptide-amidating enzyme identified. We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior andr ogen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds. Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach sta tistical significance, PAMP- or PAM-immunoreactive cells were induced after androgen-blockade therapy. In the PC-310 and PC-295 androgen-dependent mod els, PAMP or PAM NE differentiation was induced after castration in differe nt ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation. We show induction of expression of 2 new NE ma rkers in clinical specimens and xenografted PC after endocrine therapy. (C) 2001 Wiley-Liss, Inc.