The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)

• Published in: International journal of oncology Vol. 48; no. 3; pp. 861 - 868
• Main Authors: AGUILAR-ROJAS, ARTURO, PÉREZ-SOLIS, MARCO ALLAN, MAYA-NÚÑEZ, GUADALUPE
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.03.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Amino Acid Sequence; Analysis; Apoptosis; Breast Neoplasms - metabolism; cancer; Cancer therapies; Cell Membrane - metabolism; Endometrial Neoplasms - metabolism; Endoplasmic reticulum; Female; Gene expression; Gene Expression Regulation; Gonadotropin; Gonadotropin-Releasing Hormone - metabolism; Hormones - metabolism; human gonadotropin-releasing hormone receptor; Humans; Kinases; Ligands; Male; Molecular Sequence Data; Mutation; Neoplasms - metabolism; Ovarian Neoplasms - metabolism; pharmacoperone; Physiological aspects; Pituitary Gland - metabolism; Pituitary hormones; proliferation; Prostate cancer; Prostatic Neoplasms - metabolism; Protein Domains; Protein Folding; protein rescue; Proteins; Receptors, LHRH - metabolism; Reproduction; Signal Transduction; Studies
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2016.3346

Recently, an increasing amount of evidence indicates that human gonadotropin-releasing hormone (hGnRH) and its receptor (hGnRHR) are important regulatory components not only to the reproduction process but also in the regulation of some cancer cell functions such as cell proliferation, in both hormone-dependent and -independent types of tumors. The hGnRHR is a naturally misfolded protein that is retained mostly in the endoplasmic reticulum; however, this mechanism can be overcome by treatment with several pharmacoperones, therefore, increasing the amount of receptors in the cell membrane. In addition, several reports indicate that the expression level of hGnRHR in tumor cells is even lower than in pituitary or gonadotrope cells. The signal transduction pathways activated by hGnRH in both gonadotrope and different cancer cell types are described in the present review. We also discuss how the rescue of misfolded receptors in tumor cells could be a promising strategy for cancer therapy.