@article{APS4516,
author = {Heng-tong Hu and Qing-yong Ma and Dong Zhang and Su-gang Shen and Liang Han and Ya-dong Ma and Ruo-fei Li and Ke-ping Xie},
title = {HIF-1α links β-adrenoceptor agonists and pancreatic cancer cells under normoxic condition},
journal = {Acta Pharmacologica Sinica},
volume = {31},
number = {1},
year = {2016},
keywords = {},
abstract = {Aim: To examine whether β-adrenoceptor (β-AR) agonists can induce hypoxia-inducible factor (HIF)-1α accumulation which then upregulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved.
Methods: Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of β-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells.
Results: Treatment of pancreatic cancer cell lines with β-AR agonists led to accumulation of HIF-1α and then up-regulated expression of its target genes independently of oxygen levels. The induction was partly or completely inhibited not only by β-AR antagonists but also by inhibitors of PKA transduction pathways and by siHIF-1α. Both β1-AR and β2-AR agonists produced the above-mentioned effects, but β2-AR agonist was more potent.
Conclusion: Activation of β-AR receptor transactivates epidermal growth factor receptor (EGFR) and then elicites Akt and ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1α and downstream target genes independently of oxygen level. Our data suggest a novel mechanism in pancreatic cancer cells that links β-AR and HIF-1α signaling under normoxic conditions, with implications for the control of glucose transport, angiogenesis and metastasis.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4516}
}