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Article

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

  • 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
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, USA, Urology and Oncology Research Laboratories, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA, USA
  • Pages: 1373-1380
    |
    Published online on: July 25, 2012
       https://doi.org/10.3892/ijo.2012.1574
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Abstract

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, are α-, β- and γ-melanocyte-stimulating hormone and adrenocorticotropic hormone (ACTH) all of which are secreted from the anterior pituitary gland under hypothalamic control. MC2R binds ACTH but has no affinity for the other melanocortins and is, thereby, pharmacologically different from MCRs that bind those ligands. Evidence suggests that elevated GPCRs transactivate the androgen receptor (AR), the critical mediator of prostate cell growth, and consequently promote prostate cancer cell proliferation. It may be that reduced central melanocortin signaling is coincidental with reversal of prostate cancer cachexia, but no data are available on the expression of, or the role for, MCRs in prostate cancer. Here, we show that MCR (1-5) mRNAs are expressed in androgen-dependent LNCaP and androgen-independent PC3 and DU-145 human prostate cancer cell lines. Further, MC2R, the specific target of ACTH, is expressed in LNCaP, PC3 and DU-145 cells. Among the several synthetic MCR peptide ligands that we used, only ACTH promoted concentration-dependent cell proliferation in the three cell lines as shown by MTT cell proliferation assay. In LNCaP cells, the effect was additive with testosterone stimulation and was partially blunted with SHU9119, a non-selective MCR antagonist. In the same cells, ACTH induced cAMP production and increased AR nuclear labeling in immunocytochemical assays. Our observations suggest that MC2R is involved in prostate carcinogenesis and that targeting MC2R signaling may provide a novel avenue in prostate carcinoma treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Hafiz S, Dennis JC, Schwartz D, Judd R, Tao YX, Khazal K, Akingbemi B, Mo X, Abdel‑Mageed AB, Morrison E, Morrison E, et al: Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation. Int J Oncol 41: 1373-1380, 2012.
APA
Hafiz, S., Dennis, J.C., Schwartz, D., Judd, R., Tao, Y., Khazal, K. ... Mansour, M. (2012). Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation. International Journal of Oncology, 41, 1373-1380. https://doi.org/10.3892/ijo.2012.1574
MLA
Hafiz, S., Dennis, J. C., Schwartz, D., Judd, R., Tao, Y., Khazal, K., Akingbemi, B., Mo, X., Abdel‑Mageed, A. B., Morrison, E., Mansour, M."Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation". International Journal of Oncology 41.4 (2012): 1373-1380.
Chicago
Hafiz, S., Dennis, J. C., Schwartz, D., Judd, R., Tao, Y., Khazal, K., Akingbemi, B., Mo, X., Abdel‑Mageed, A. B., Morrison, E., Mansour, M."Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation". International Journal of Oncology 41, no. 4 (2012): 1373-1380. https://doi.org/10.3892/ijo.2012.1574
Copy and paste a formatted citation
x
Spandidos Publications style
Hafiz S, Dennis JC, Schwartz D, Judd R, Tao YX, Khazal K, Akingbemi B, Mo X, Abdel‑Mageed AB, Morrison E, Morrison E, et al: Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation. Int J Oncol 41: 1373-1380, 2012.
APA
Hafiz, S., Dennis, J.C., Schwartz, D., Judd, R., Tao, Y., Khazal, K. ... Mansour, M. (2012). Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation. International Journal of Oncology, 41, 1373-1380. https://doi.org/10.3892/ijo.2012.1574
MLA
Hafiz, S., Dennis, J. C., Schwartz, D., Judd, R., Tao, Y., Khazal, K., Akingbemi, B., Mo, X., Abdel‑Mageed, A. B., Morrison, E., Mansour, M."Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation". International Journal of Oncology 41.4 (2012): 1373-1380.
Chicago
Hafiz, S., Dennis, J. C., Schwartz, D., Judd, R., Tao, Y., Khazal, K., Akingbemi, B., Mo, X., Abdel‑Mageed, A. B., Morrison, E., Mansour, M."Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation". International Journal of Oncology 41, no. 4 (2012): 1373-1380. https://doi.org/10.3892/ijo.2012.1574
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