Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches

Molecules

Zsuzsanna Szabo¹  Gabor Halmos¹  Zoltan Hernadi²  Sandor Huga²  Balazs Dezso³  Eva Juhasz⁴  Csongor Kiss⁴  Andrew V. Schally⁵ 

[1] Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary;Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;Department of Pathology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary;Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, Miami, FL 33125, USA;

关键词: GHRH;    receptors for GHRH;    splice variants;    human endometrial carcinoma;   

DOI  :  10.3390/molecules27092671

来源: DOAJ

【 摘 要 】

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.

【 授权许可】

Unknown