Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation

• DOI: 10.3892/ijo.2012.1574
• Publication Date: 2012-07-25T11:08:01Z
• Authors: SALY HAFIZ; JOHN C. DENNIS; DEAN SCHWARTZ; ROBERT JUDD; YA-XIONG TAO; KAMEL KHAZAL; BENSON AKINGBEMI; XIU-LEI MO; ASIM B. ABDEL-MAGEED; EDWARD MORRISON; MAHMOUD MANSOUR
• Keywords: Melanocortins; ACTH receptor

The melanocortin receptors (MCRs 1-5) are G protein coupled-receptors (GPCRs) that regulate food intake, inflammation, skin pigmentation, sexual function and steroidogenesis. Their peptide ligands, the melanocortins, α-, β- γ-melanocyte-stimulating hormone adrenocorticotropic (ACTH) all of which secreted from anterior pituitary gland under hypothalamic control. MC2R binds ACTH but has no affinity for other melanocortins is, thereby, pharmacologically different MCRs bind those ligands. Evidence suggests elevated GPCRs transactivate androgen receptor (AR), critical mediator prostate cell growth, consequently promote cancer proliferation. It may be reduced central signaling is coincidental with reversal cachexia, data available on expression of, or role for, in cancer. Here, we show MCR (1-5) mRNAs expressed androgen-dependent LNCaP androgen-independent PC3 DU-145 human lines. Further, MC2R, specific target ACTH, LNCaP, cells. Among several synthetic ligands used, only promoted concentration-dependent proliferation three lines as shown by MTT assay. In cells, effect was additive testosterone stimulation partially blunted SHU9119, a non-selective antagonist. same induced cAMP production increased AR nuclear labeling immunocytochemical assays. Our observations suggest involved carcinogenesis targeting provide novel avenue carcinoma treatment.