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

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 f...

Full description

Bibliographic Details
Main Authors:	Subramani, Ramadevi, Lopez-Valdez, Rebecca, Salcido, Alyssa, Boopalan, Thiyagarajan, Arumugam, Arunkumar, Nandy, Sushmita, Lakshmanaswamy, Rajkumar
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221692/

id	pubmed-4221692
recordtype	oai_dc
spelling	pubmed-42216922014-11-06 Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma Subramani, Ramadevi Lopez-Valdez, Rebecca Salcido, Alyssa Boopalan, Thiyagarajan Arumugam, Arunkumar Nandy, Sushmita Lakshmanaswamy, Rajkumar Original Article 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. Nature Publishing Group 2014-10 2014-10-10 /pmc/articles/PMC4221692/ /pubmed/25301264 http://dx.doi.org/10.1038/emm.2014.61 Text en Copyright © 2014 KSBMB. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Subramani, Ramadevi Lopez-Valdez, Rebecca Salcido, Alyssa Boopalan, Thiyagarajan Arumugam, Arunkumar Nandy, Sushmita Lakshmanaswamy, Rajkumar
spellingShingle	Subramani, Ramadevi Lopez-Valdez, Rebecca Salcido, Alyssa Boopalan, Thiyagarajan Arumugam, Arunkumar Nandy, Sushmita Lakshmanaswamy, Rajkumar Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
author_facet	Subramani, Ramadevi Lopez-Valdez, Rebecca Salcido, Alyssa Boopalan, Thiyagarajan Arumugam, Arunkumar Nandy, Sushmita Lakshmanaswamy, Rajkumar
author_sort	Subramani, Ramadevi
title	Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
title_short	Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
title_full	Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
title_fullStr	Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
title_full_unstemmed	Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
title_sort	growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma
description	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.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221692/
_version_	1613152769197211648

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

Similar Items