Veterans Affairs Medical Center, South Florida Veterans Affairs Foundation for Research and Education, Miami, 33125, USA.
Cell Mol Life Sci. 2010 Mar;67(6):959-64. doi: 10.1007/s00018-009-0224-y. Epub 2009 Dec 13.
Growth hormone-releasing hormone (GHRH) can act as a potent growth factor in various cancers. The mitogenic activity of this neuropeptide is exerted through binding to the pituitary type receptors (GHRH-R) or their splice variants (SV). In the present work, we studied whether this hormone can activate the JAK2/STAT3 pathway which plays a crucial role in cancer cell proliferation and is also linked to carcinogenesis. We transfected HeLa human cervical cancer cells, which are not sensitive to GHRH analogs with the pGHRH-R. Transfected cells responded to the GHRH or its antagonist with an increase or a decrease in proliferation, respectively. These results were confirmed by the expression of proliferating cell nuclear antigen. We then showed that these effects are linked to the activation of the JAK2/STAT3 pathway. Our work demonstrates the activation of JAK/STAT3 pathway by GHRH and sheds further light to the mechanisms of the antitumorogenic action of GHRH antagonists.
生长激素释放激素 (GHRH) 可以作为各种癌症中的一种有效的生长因子。这种神经肽的有丝分裂活性是通过与垂体型受体 (GHRH-R) 或其剪接变体 (SV) 结合来发挥的。在本工作中，我们研究了这种激素是否可以激活 JAK2/STAT3 途径，该途径在癌细胞增殖中起着至关重要的作用，并且与致癌作用有关。我们用 pGHRH-R 转染对 GHRH 类似物不敏感的人宫颈癌细胞系 HeLa。转染的细胞对 GHRH 或其拮抗剂的反应分别是增殖增加或减少。增殖细胞核抗原的表达证实了这些结果。然后我们表明这些作用与 JAK2/STAT3 途径的激活有关。我们的工作证明了 GHRH 激活 JAK/STAT3 途径，并进一步阐明了 GHRH 拮抗剂的抗肿瘤作用机制。
