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-beta and cyclo-oxygenease-2. Altogether, GHR silencing controls the
growth and
metastasis of
pancreatic cancer and reveals its importance in
pancreatic cancer pathogenesis.