Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma

• Published in: Experimental & molecular medicine pp. 1 - 11
• Main Authors: Ramadevi Subramani, Rebecca Lopez-Valdez, Alyssa Salcido, Thiyagarajan Boopalan, Arunkumar Arumugam, Sushmita Nandy, Rajkumar Lakshmanaswamy
• Format: Journal Article
• Language: English
• Published: 생화학분자생물학회 01.10.2014
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-relateddeath. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and thispathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, todate there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interferenceapproach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growthand metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHRis upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition ofGHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming abilityand reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signalregulatedkinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling,as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-βand cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals itsimportance in pancreatic cancer pathogenesis. KCI Citation Count: 16