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

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 anti...

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Bibliographic Details
Published in:Regulatory peptides 2002-10, Vol.108 (2), p.47-53
Main Authors: Busto, R, Schally, A.V, Braczkowski, R, Plonowski, A, Krupa, M, Groot, K, Armatis, P, Varga, J.L
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
Anticancer drugs
Autocrine growth factors
Base Sequence
Biological and medical sciences
Bone Neoplasms - genetics
Diseases of the osteoarticular system
DNA Primers
Genetic Variation
GHRH
GHRH antagonists
GHRH receptors
Gonadotropin-Releasing Hormone - genetics
Human malignant bone tumors
Humans
Male
Medical sciences
Mice
Mice, Nude
Osteosarcoma - genetics
Receptors, LHRH - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Sarcoma - genetics
Transplantation, Heterologous
Tumor Cells, Cultured
Tumors of striated muscle and skeleton
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Summary: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 SV 1 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 SV 1 of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV 1 of GHRH receptors on tumoral cells.
ISSN:0167-0115
1873-1686
DOI:10.1016/S0167-0115(02)00109-X