Luteinizing hormone-releasing hormone agonists interfere with the stimulatory actions of epidermal growth factor in human prostatic cancer cell lines, LNCaP and DU 145

• Published in: The journal of clinical endocrinology and metabolism Vol. 81; no. 11; pp. 3930 - 3937
• Main Authors: MORETTI, R. M, MONTAGNANI MARELLI, M, DONDI, D, POLETTI, A, MARTINI, L, MOTTA, M, LIMONTA, P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-11-1996
• Subjects: Biological and medical sciences; Cell Division - drug effects; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; Gene Expression - drug effects; Genes, fos - drug effects; Gonadotropin-Releasing Hormone - agonists; Humans; Male; Medical sciences; Nephrology. Urinary tract diseases; Phosphorylation; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptor, Epidermal Growth Factor - drug effects; Receptor, Epidermal Growth Factor - metabolism; Tumor Cells, Cultured; Tumors of the urinary system; Tyrosine - metabolism; Urinary tract. Prostate gland; Human; Cell proliferation; Agonist; Urinary system disease; Prostate disease; Cytokine; Peptide hormone; Gonadotropin RH; Male; Malignant tumor; Hypothalamic hormone; Chemotherapy; Epidermal growth factor; Treatment; Polypeptide; Metabolic interrelation; Biological effect; Hormone releasing factor; Male genital diseases; Prostate; Tumor cell; Growth factor; Quantitative analysis
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.81.11.3930

LH-releasing hormone (LHRH) agonists exert a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present studies were aimed at clarifying whether these compounds might exert their antiproliferative action by interfering with the stimulatory action of epidermal growth factor (EGF). To this purpose, the effects of a LHRH agonist (Zoladex, LHRH-A) on the mitogenic action of EGF, on some of the EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of the 170-kDa EGF receptor, and c-fos protooncogene expression), as well as on the concentration of EGF receptors have been evaluated. These studies have been performed in both LNCaP and DU 145 cells. The results obtained show that in LNCaP cells, LHRH-A counteracts the mitogenic action of EGF, completely abrogates EGF-induced c-fos expression, and significantly reduces the concentration of EGF-binding sites. The EGF-activated tyrosine phosphorylation of the EGF receptor is not affected by LHRH-A in LNCaP cells. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits the tyrosine phosphorylation of the EGF receptor induced by EGF, and significantly reduces the number of EGF-binding sites. In these cells, LHRH-A is not able to modify the increased expression of c-fos that follows the treatment with EGF. These data suggest that LHRH agonists may inhibit the proliferation of human prostatic tumor cells by interfering with the stimulatory actions of EGF. The intracellular mechanism of action of these compounds appears to differ in androgen-dependent LNCaP and androgen-independent DU 145 cells.