title: Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma.
abstract: Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and 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 signal-regulated kinase, 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-β and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis.
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Ramadevi
authors.initials: R
authors.lastname: Subramani
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lopez-Valdez
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Salcido
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Boopalan
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Nandy
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences MSB1, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, El Paso, TX, USA.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Lakshmanaswamy
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D011986:Receptors, Somatotropin