Agnieszka Siejka Andrew V. Schally +1-305-5753477 +1-305-5757279 Andrew.Schally@va.gov Nektarios Barabutis +1-305-5753477 +1-305-5757279 nbarabutis@gmail.com Veterans Affairs Medical Center, South Florida Veterans Affairs Foundation for Research and Education Miami FL 33125 USA Divisions of Hematology/Oncology and Endocrinology, Department of Medicine University of Miami, Miller School of Medicine Miami FL 33125 USA Department of Pathology, Department of Medicine University of Miami, Miller School of Medicine Miami FL 33125 USA Research Service (151), Veterans Affairs Medical Center 1201 Northwest 16th Street Miami FL 33125 USA Abstract 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.
/lp/springer-journals/activation-of-janus-kinase-signal-transducer-and-activator-of-9lgF9Kl80D