Activation of Janus kinase/signal transducer and activator of transcription 3 pathway by growth hormone-releasing hormone.
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.
Siejka
Agnieszka
A
Veterans Affairs Medical Center, South Florida Veterans Affairs Foundation for Research and Education, Miami, 33125, USA.
Schally
Andrew V
AV
Barabutis
Nektarios
N
D049109:Cell Proliferation / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013007:Growth Hormone-Releasing Hormone; D053612:Janus Kinases; C048250:somatotropin releasing hormone receptor