Fast, Stable Induction of P-Glycoprotein-mediated Drug Resistance in BT-474 Breast Cancer Cells by Stable Transfection of ABCB1 Gene.

Yuan Tang, Yue Wang, Sudhir Deosarkar, Fariborz Soroush, Mohammad F Kiani, Bin Wang

Index: Anticancer Res. 35 , 2531-8, (2015)

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Abstract

Patients with P-glycoprotein and HER2/neu (HER2) receptor-overexpressing breast cancer usually have poor clinical outcomes. However, there exist no commercially available breast cancer cell lines that are HER2/P-glycoprotein double-positive, which limits research in this field.We report on the development and characterization of a drug-resistant sub-line from an HER2-positive breast cancer cell line by stable transfection of the ATP-binding cassette (ABC) subfamily B member 1 (ABCB1) gene which encodes P-glycoprotein.ABCB1 gene expression levels were higher after transfection, which led to a 40-fold increase in P-glycoprotein expression. Interestingly, the transfection of ABCB1 also led to a slight increase in HER2 gene and protein expression levels. The transfection of ABCB1 increased the P-glycoprotein expression levels significantly.The method used herein for developing this cell line is appropriate for fast, stable induction of P-glycoprotein-mediated drug resistance compared to traditional methods. The in vitro cytotoxicity test suggests this cell line has cross-resistance to a wide range of chemotherapeutic agents.Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.