PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) IS AN EPIDERMAL GROWTH FACTOR-REGULATED SECRETORY PRODUCT OF HUMAN PROSTATIC EPITHELIAL-CELLS

Parathyroid hormone-related protein (PTHrP) has previously been shown to be expressed in human prostatic tissue and in prostatic cancer cell lines. In the present study, PTHrP immunoreactivity was detected in t he glandular epithelium of normal prostate and benign prostatic hyperp lasia (BPH), as well as in prostatic adenocarcinoma (CaP). Epithelial cell cultures derived from normal, BPH, and CaP tissues were also stai ned by antibodies against PTHrP, and northern analysis revealed multip le transcripts of PTHrP in the cellular RNA. PTHrP (1-34) was measurab le by radioimmunoassay (RIA) in media conditioned by the prostatic epi thelial cell cultures, and PTHrP accumulated in conditioned media duri ng a 72 hr time course, Addition of complete growth medium to starved cells resulted in increased PTHrP mRNA levels by 1 hr, with maximal st imulation at 8-24 kr. Several individual factors contained in the comp lete growth medium were tested for their ability to regulate PTHrP exp ression. Epidermal growth factor (EGF) was the major inducer of PTHrP expression, while cholera toxin, bovine pituitary extract, hydrocortis one, and insulin had minimal or no effect on PTHrP transcript levels, Since each of these factors is growth stimulatory, the unique ability of EGF to induce PTHrP is apparently unrelated to mitogenicity, 1,25-D ihydroxyvitamin D-3 [1,25(OH)(2)D-3], an inhibitor of PTHrP expression in several other cell types, had no effect on steady-state levels of PTHrP mRNA expressed by epithelial cells in complete growth medium, al though prostate cells have vitamin D receptors and are responsive to 1 ,25(OH)(2)D-3 in other ways. Our results indicate that PTHrP expressio n is not confined to the neuroendocrine cells of the human prostate an d that our culture system can be used as a model to investigate the ro le of PTHrP in the prostate. (C) 1996 Wiley-Liss, Inc.