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首页> 外文期刊>Regulatory peptides. >Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors.
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Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors.

机译：人类恶性骨肿瘤中生长激素释放激素和GHRH受体剪接变体的mRNA表达。

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摘要

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.
机译：生长激素释放激素（GHRH）受体的剪接变体（SV）已发现在几种人类癌细胞系中。 GHRH拮抗剂抑制各种人类癌症的生长，包括骨肉瘤和尤因氏肉瘤，异种移植到裸鼠中或体外培养，它们的抗增殖作用可以部分通过这些GHRH受体的介导。在这项研究中，我们发现人类骨肉瘤细胞系MNNG / HOS和SK-ES-1 Ewing肉瘤细胞系中GHRH受体的SV（1）亚型的mRNA。我们还检测到了GHRH的mRNA，该mRNA显然翻译成GHRH肽并由细胞分泌，如在细胞培养条件培养基中存在GHRH样免疫反应性所示。在体外增殖研究中，GHRH拮抗剂JV-1-38和抗人GHRH的抗血清剂量依赖性地抑制SK-ES-1和MNNG / HOS细胞的生长。我们的研究表明人类肉瘤中存在基于GHRH和GHRH受体的SV（1）的自分泌刺激环。 GHRH拮抗剂对恶性骨肿瘤的直接抗增殖作用似乎是通过肿瘤细胞上GHRH受体的SV（1）发挥的。

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