The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas

Rebeca Busto, Andrew V Schally, Jozsef L. Varga, M. Olga Garcia-Fernandez, Kate Groot, Patricia Armatis, Karoly Szepeshazi

Research output: Contribution to journalArticle

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Abstract

Splice variants (SVs) of receptors for growth hormone-releasing hormone (GHRH) have been found in primary human prostate cancers and diverse human cancer cell lines. GHRH antagonists inhibit growth of various experimental human cancers, including pancreatic and colorectal, xenografted into nude mice or cultured in vitro, and their antiproliferative action could be mediated in part through SVs of GHRH receptors. In this study we examined the expression of mRNA for GHRH and for SVs of its receptors in tumors of human pancreatic, colorectal, and gastric cancer cell lines grown in nude mice. mRNA for both GHRH and SV1 isoform of GHRH receptors was expressed in tumors of pancreatic (SW1990, PANC-1, MIA PaCa-2, Capan-1, Capan-2, and CFPAC1), colonic (COLO 320DM and HT-29), and gastric (NCI-N87, HS746T, and AGS) cancer cell lines; mRNA for SV2 was also present in Capan-1, Capan-2, CFPAC1, HT-29, and NCI-N87 tumors. In proliferation studies in vitro, the growth of pancreatic, colonic, and gastric cancer cells was stimulated by GHRH(1-29)NH2 and inhibited by GHRH antagonist JV-1-38. The stimulation of some gastroenteropancreatic cancer cells by GHRH was followed by an increase in cAMP production, and GHRH antagonist JV-1-38 competitively inhibited this effect. Our study indicates the presence of an autocrine/paracrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human pancreatic, colorectal, and gastric cancers. The finding of SV1 receptor in human cancers provides an approach to an antitumor therapy based on the blockade of this receptor by specific GHRH antagonists.

Original languageEnglish
Pages (from-to)11866-11871
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number18
DOIs
StatePublished - Sep 3 2002
Externally publishedYes

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Growth Hormone-Releasing Hormone
Carcinoma
Hormone Antagonists
Pancreatic Neoplasms
Neoplasms
Stomach Neoplasms
Colorectal Neoplasms
Nude Mice
Cell Line
Messenger RNA
Somatotropin Receptors
Growth
Colonic Neoplasms
Prostatic Neoplasms
Stomach
Protein Isoforms
somatotropin releasing hormone receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas. / Busto, Rebeca; Schally, Andrew V; Varga, Jozsef L.; Garcia-Fernandez, M. Olga; Groot, Kate; Armatis, Patricia; Szepeshazi, Karoly.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 18, 03.09.2002, p. 11866-11871.

Research output: Contribution to journalArticle

Busto, Rebeca ; Schally, Andrew V ; Varga, Jozsef L. ; Garcia-Fernandez, M. Olga ; Groot, Kate ; Armatis, Patricia ; Szepeshazi, Karoly. / The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 18. pp. 11866-11871.
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AU - Garcia-Fernandez, M. Olga

AU - Groot, Kate

AU - Armatis, Patricia

AU - Szepeshazi, Karoly

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