Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors
| Autor: | Artur Plonowski, Jozsef L. Varga, Kate Groot, R Busto, R Braczkowski, Magdalena Krupa, Patricia Armatis, Andrew V. Schally |
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| Rok vydání: | 2002 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Physiology Transplantation Heterologous Clinical Biochemistry Mice Nude Bone Neoplasms Biology Biochemistry Gonadotropin-Releasing Hormone Mice Cellular and Molecular Neuroscience Endocrinology Internal medicine Tumor Cells Cultured medicine Animals Humans RNA Messenger Autocrine signalling Receptor DNA Primers Osteosarcoma Base Sequence Reverse Transcriptase Polymerase Chain Reaction Genetic Variation Sarcoma Growth hormone–releasing hormone medicine.disease In vitro Transplantation Alternative Splicing Cell culture Receptors LHRH hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Regulatory Peptides. 108:47-53 |
| ISSN: | 0167-0115 |
| DOI: | 10.1016/s0167-0115(02)00109-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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