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 neuroendocrine tumors do not respond to androgen ablation therapy. The regulation of synthesis of chromogranins and their processing into neuropeptides have not yet been studied in neuroendocrine cells of the prostate. We used CRL-5813 cells which were derived from a metastasis from small-cell prostate cancer for studies on steroid receptor expression and 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 factor (bFGF).

RESULTS

cDNA fragments for alpha-estrogen receptor and androgen receptor but not for beta-estrogen receptor, progesterone receptor, and glucocorticoid receptor were amplified from CRL-5813 cells. These cells were found to contain typical markers of large dense-core vesicles, i.e., chromogranins A and B and secretogranin II. Forskolin significantly stimulated the synthesis and secretion of the chromogranin B-derived peptide PE-11 and the secretogranin II-derived secretoneurin. bFGF significantly induced PE-11 protein levels in cell extracts. CONCLUSIONS. Our results demonstrate the expression of typical large dense-core vesicle proteins, i.e., chromogranins, in a small-cell prostate cancer cell line and their upregulation by a protein kinase A activator and, in part, by bFGF.