PRESENCE OF CHROMOGRANINS AND REGULATION OF THEIR SYNTHESIS AND PROCESSING IN A NEUROENDOCRINE PROSTATE TUMOR-CELL LINE

BACKGROUND. Small-cell carcinoma and carcinoid tumors of the prostate display a neuroendocrine phenotype. To some extent, adenocarcinomas of the prostate also express neuroendocrine properties. Prostatic neuroe ndocrine tumors do not respond to androgen ablation therapy. The regul ation of synthesis of chromogranins and their processing into neuropep tides have not yet been studied in neuroendocrine cells of the prostat e. We used CRL-5813 cells which were derived from a metastasis from sm all-cell prostate cancer for studies on steroid receptor expression an d chromogranin processing. METHODS. The expression of steroid receptor mRNA in CRL-5813 cells was examined by polymerase chain reaction. The synthesis and secretion of chromogranin- and secretogranin II-derived peptides were investigated by radioimmunoassays and high-performance liquid chromatography in untreated cells and in cells treated with the protein kinase A activator forskolin or basic fibroblast growth fatte r (bFGF). RESULTS. cDNA fragments for alpha-estrogen receptor and andr ogen receptor but not for beta-estrogen receptor, progesterone recepto r, and glucocorticoid receptor were amplified from CRL-5813 cells. The se cells were found to contain typical markers of large dense-core ves icles, i.e., chromogranins A and B and secretogranin II. Forskolin sig nificantly stimulated the synthesis and secretion of the chromogranin B-derived peptide PE-11 and the secretogranin II-derived secretoneurin . bFGF significantly induced PE-12 protein levels in cell extracts. CO NCLUSIONS. Our results demonstrate the expression of typical large den se-core vesicle proteins, i.e., chromogranins, in a small-cell prostat e cancer cell line and their upregulation by a protein kinase A activa tor and, in part, by bFGF. Prostate Supplement 8:80-87, 1998. (C) 1998 Wiley-Liss, Inc.