Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor

Hippokratis Kiaris, Ioulia Chatzistamou, Andrew V Schally, Gabor Halmos, Jozsef L. Varga, Helen Koutselini, Anastasios Kalofoutis

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Existing evidence indicates that, in addition to its neuroendocrine action, growth hormone-releasing hormone (GHRH) acts directly on several nonpituitary tissues, especially neoplasms, and stimulates cell proliferation. We have recently reported that a splice variant of the receptor (SV1) is expressed in various normal tissues and particularly in tumor tissues, producing mitogenic effects on GHRH binding. By using HEC-1A human endometrial carcinoma cells, which express endogenous SV1, we show that, in addition to its ability to mediate the mitogenic effects of GHRH, SV1 also possesses relatively high intrinsic, ligand-independent activity. By using an antisense RNA-based approach we found that SV1 ablation reduces the efficacy of colony formation and the rate of cell proliferation of HEC-1A cells in the absence of exogenous GHRH, and decreases their sensitivity to GHRH when the neurohormone is added to the culture media. This ligand-independent stimulation of cell proliferation appears to be a characteristic property of the truncated form of the receptor, because the expression of SV1 and not of the full-length GHRH receptor stimulated the proliferation of 3T3 fibroblasts in the absence of exogenous GHRH, whereas both forms mediated the proliferative effects of GHRH. Evaluation of 21 specimens of human primary endometrial carcinoma for expression of SV1 by immunohistochemistry indicated that in contrast to the GHRH receptor, which is absent, SV1 is expressed in ≈43% of the specimens. These findings indicate that SV1 can operate in a ligand-independent as well as a ligand-dependent manner. The overexpression of this form of GHRH receptor may be associated with carcinogenesis.

Original languageEnglish
Pages (from-to)9512-9517
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number16
DOIs
StatePublished - Aug 5 2003
Externally publishedYes

Fingerprint

Growth Hormone-Releasing Hormone
Ligands
Cell Proliferation
Endometrial Neoplasms
Antisense RNA
somatotropin releasing hormone receptor
Neurotransmitter Agents
Culture Media
Neoplasms
Carcinogenesis
Fibroblasts
Immunohistochemistry

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor. / Kiaris, Hippokratis; Chatzistamou, Ioulia; Schally, Andrew V; Halmos, Gabor; Varga, Jozsef L.; Koutselini, Helen; Kalofoutis, Anastasios.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 16, 05.08.2003, p. 9512-9517.

Research output: Contribution to journalArticle

Kiaris, Hippokratis ; Chatzistamou, Ioulia ; Schally, Andrew V ; Halmos, Gabor ; Varga, Jozsef L. ; Koutselini, Helen ; Kalofoutis, Anastasios. / Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 16. pp. 9512-9517.
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