Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

Kuang,Yehong; Wang,Shouman; Tang,Lili; Hai,Jian; Yan,Guojiao; Liao,Liqiu

doi:10.3892/ol.2018.8199

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

Authors:
- Yehong Kuang
- Shouman Wang
- Lili Tang
- Jian Hai
- Guojiao Yan
- Liqiu Liao
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Affiliations: Department of Dermatology, Hunan Clinical Meditech Research Center for Breast Cancer, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Breast Surgery, Hunan Clinical Meditech Research Center for Breast Cancer, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: March 7, 2018 https://doi.org/10.3892/ol.2018.8199
Pages: 7279-7290

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Abstract

Vacuolar H+‑ATPase (V‑ATPase) serves a key role in adjusting and maintaining the intracellular pH, as well as in regulating the drug resistance of tumor cells. In recent years, the expression level of V‑ATPase has been considered to be able to predict the sensitivity of breast cancer cells to chemotherapy drugs. Cluster of differentiation 147 (CD147) is known to serve a key role in the development and progression of breast cancer. The present study aimed to identify the role CD147 and V‑ATPase in chemoresistance in breast cancer, and to characterize the regulation of CD147 on V‑ATPase. Firstly, the expression levels of CD147 and V‑ATPase were detected in chemotherapy‑resistance breast cancer samples. It was demonstrated that V‑ATPase was highly expressed in chemotherapy‑resistance breast cancer samples, and that its expression was correlated with CD147 expression. Subsequently, MCF‑7 and MDA‑MB‑231 cells were used to study the regulatory effect of CD147 on the expression and function of V‑ATPase. Gene transfection or small interfering RNA transfection were used to control the expression of CD147 in the two cell lines. The results revealed that the overexpression of CD147 increased the expression of V‑ATPase in MCF‑7 cells, whereas CD147 knockdown decreased V‑ATPase expression in MDA‑MB‑231 cells. It was also observed that CD147 affected the V‑ATPase activity, regulating the transmembrane pH gradient of cancer cells. These results demonstrated that CD147 was associated with the sensitivity of chemotherapeutic drugs of epirubicin and docetaxel, while pantoprazole was able to partially reverse the CD147‑mediated chemoresistance in breast cancer. Therefore, the current study provided a possible mechanism for further examination of drug resistance in breast cancer.

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