Activation of Janus kinase/signal transducer and activator of transcription 3 pathway by growth hormone-releasing hormone

作者:Siejka Agnieszka; Schally Andrew V*; Barabutis Nektarios
来源:Cellular and Molecular Life Sciences, 2010, 67(6): 959-964.
DOI:10.1007/s00018-009-0224-y

摘要

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.

  • 出版日期2010-3