Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers

Artur Plonowski, Andrew V. Schally, Rebeca Busto, Magdalena Krupa, Jozsef L. Varga, Gabor Halmos

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors in LNCaP, MDA-PCa-2b and PC-3 human prostate cancers grown in nude mice was investigated by RT-PCR. The expression of mRNA for GHRH was detected in LNCaP and PC-3, but not in MDA-PCa-2b prostatic carcinoma. RT-PCR analyses of mRNA isolated from LNCaP, MDA-PCa-2b and PC-3 cancers, revealed the presence of 720 and 566bp products, corresponding to SV1 and SV2 isoforms of GHRH receptors. In PC-3 tumor membranes a radiolabeled GHRH antagonist [125I]-JV-1-42 was bound to one class of high-affinity binding sites (Kd=1.81±0.47nM) and maximum binding capacity of 332.7±27.8fmol/mg membrane protein. The in vivo uptake of [125I]-JV-1-42 was observed in all xenografts of human prostate cancer, the tracer accumulation being the highest in PC-3 tumors. These results indicate that GHRH and SVs of its receptors, different from those found in the pituitary, are present in experimental human prostate cancers and may form a local mitogenic loop. The antiproliferative effects of GHRH antagonists on growth of prostate cancer could be exerted in part by an interference with this local GHRH system.

Original languageEnglish (US)
Pages (from-to)1127-1133
Number of pages7
JournalPeptides
Volume23
Issue number6
DOIs
StatePublished - Jul 30 2002

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Keywords

  • Growth hormone-releasing hormone
  • Prostate cancer
  • Receptors for growth hormone-releasing hormone

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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