Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors

R. Busto, Andrew V Schally, R. Braczkowski, A. Plonowski, M. Krupa, K. Groot, P. Armatis, J. L. Varga

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV1 isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV1 of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV1 of GHRH receptors on tumoral cells.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalRegulatory Peptides
Volume108
Issue number2-3
DOIs
StatePublished - Oct 15 2002
Externally publishedYes

Fingerprint

Growth Hormone-Releasing Hormone
Tumors
Bone
Bone and Bones
Messenger RNA
Hormone Antagonists
Neoplasms
Methylnitronitrosoguanidine
Ewing's Sarcoma
Osteosarcoma
RNA Isoforms
Human Growth Hormone
somatotropin releasing hormone receptor
Conditioned Culture Medium
Growth
Cell culture
Nude Mice
Sarcoma
Immune Sera
Protein Isoforms

Keywords

  • Anticancer drugs
  • Autocrine growth factors
  • GHRH
  • GHRH antagonists
  • GHRH receptors
  • Human malignant bone tumors

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors. / Busto, R.; Schally, Andrew V; Braczkowski, R.; Plonowski, A.; Krupa, M.; Groot, K.; Armatis, P.; Varga, J. L.

In: Regulatory Peptides, Vol. 108, No. 2-3, 15.10.2002, p. 47-53.

Research output: Contribution to journalArticle

Busto, R. ; Schally, Andrew V ; Braczkowski, R. ; Plonowski, A. ; Krupa, M. ; Groot, K. ; Armatis, P. ; Varga, J. L. / Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors. In: Regulatory Peptides. 2002 ; Vol. 108, No. 2-3. pp. 47-53.
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