Hypoxia regulates ABCG2 activity through the activivation of ERK1/2/HIF-1α and contributes to chemoresistance in pancreatic cancer cells

Cancer Biology & Therapy
Xiaodan HeXiaohong Shen

Abstract

Pancreatic cancer is a drug resistant hypovascular tumor. Although there are many studies on the mechanism of chemoresistance in pancreatic cancers, studies on the relationship between ABCG2 and chemoresistance during hypoxia of pancreatic cancer are rare. Hypoxia-inducible factor-1 (HIF-1α) is a master regulator of the transcriptional response to oxygen deprivation in cancer cells. The aim of this study was to examine the role of ABCG2 and HIF-1α in mediating chemoresistance during hypoxia in pancreatic cancer. In this study, we detected the expression levels of ABCG2, ERK/phosphorylated-ERK (p-ERK) and HIF-1α by immunohistochemistry in fresh pancreatic cancer and paracarcinoma tissues obtained from 25 patients. The mechanism by which p-ERK1/2 and HIF-1α affect ABCG2s expression was analyzed in the hypoxic cultured human pancreatic cancer cell line Capan-2. ABCG2-mediatedregulation of gemcitabine response under hypoxic conditions in pancreatic cancer cells was observed. It was found that ABCG2, ERK/p-ERK and HIF-1α were overexpressed in cancer tissues. ABCG2, HIF-1α and p-ERK levels were demonstrated to be high during hypoxic conditions in pancreatic cancer cells. Hypoxia induced phosphorylation of ERK1/2 to activate HIF-1α an...Continue Reading

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Citations

Jul 8, 2018·International Journal of Cancer. Journal International Du Cancer·Xiaoyang HouYanqun Liu
Apr 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Taranjit S Gujral, Marc W Kirschner
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Jan 14, 2021·Journal of Hematology & Oncology·Jinxin TaoYupei Zhao
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Sep 30, 2021·Cellular and Molecular Life Sciences : CMLS·Samiksha KukalRitushree Kukreti

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Methods Mentioned

BETA
pancreatectomy
nuclear translocation
flow cytometry
transfection
PCR
Fluorescence
Immunoprecipitation

Software Mentioned

SPSS
Meta Morph
Flow Jo

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