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β2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway

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Abstract

Psychological stress has been recognized as a well-documented risk factor associated with β2-adrenergic receptor (β2-AR) in the development of pancreatic cancer. Aldo–keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of β2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and β2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing β2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of β2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased β2-AR levels and increased that of p-ERK1/2. Taken together, β2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the β2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (Grant Nos. 81472272 and 81602114), Natural Science Foundation of Jiangsu Province (Grant No. BK20161286), Postdoctoral Science Foundation of China (Grant No. 2017M620221), and Social Development Foundation of Nantong City (Grant Nos. MS22016056, and MS12017002-6).

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  1. Ming-Bing Xiao and Dan-Dan Jin have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Road, Suzhou, 215006, Jiangsu, People’s Republic of China

    Ming-Bing Xiao & Wei-Chang Chen

  2. Department of Gastroenterology, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, People’s Republic of China

    Ming-Bing Xiao, Dan-Dan Jin, Yu-Jie Jiao, Wen-Kai Ni, Jin-Xia Liu, Li-Shuai Qu, Cui-Hua Lu, Run-Zhou Ni & Feng Jiang

  3. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, People’s Republic of China

    Ming-Bing Xiao

  4. Clinical Medicine, Medical College, Nantong University, No. 9, Seyuan Road, Nantong, 226001, People’s Republic of China

    Dan-Dan Jin & Yu-Jie Jiao

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  1. Ming-Bing Xiao
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Xiao, MB., Jin, DD., Jiao, YJ. et al. β2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway. Mol Biol Rep 45, 1863–1871 (2018). https://doi.org/10.1007/s11033-018-4332-3

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