Co-expression of cytokeratin 8 and breast cancer resistant protein indicates a multifactorial drug-resistant phenotype in human breast cancer cell line

Life Sciences
Fang LiuDongsheng Xiong

Abstract

The aim was to determine whether increased CK8 and BCRP expression cooperatively contribute to multidrug resistance (MDR) in MCF-7/MX cells. Accumulating evidence suggests that the development and maintenance of cancer MDR involves complex multimodal mechanisms that interact concomitantly and complementarily. In this report, we observed elevated expression of cytokeratin 8 (CK8) in MCF-7/MX, a mitoxantrone (MX)-selected human breast tumor cell line with the MDR phenotype known as overexpression of breast cancer resistant protein (BCRP). Gene transfection methods were used to express CK8 and BCRP in NIH3T3 fibroblasts, individually or in combination. Taken together, our present study suggests that CK8 together with BCRP may play significant roles in conferring the multifactorial MDR phenotype of MCF-7/MX cells, but may act independently via potentially different mechanisms. Although expressing either CK8 or BCRP alone was able to confer resistance to mitoxantrone, cells co-expressing both proteins demonstrated significantly increased drug resistance. Furthermore, RNAi knockdown of CK8 and BCRP, alone and in combination, in MCF-7/MX cells significantly attenuated their resistance to chemotherapeutic agents. Interestingly, in cont...Continue Reading

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Citations

Nov 1, 2011·Human Molecular Genetics·Julien ColasAleksander Edelman
Apr 19, 2013·Experimental Hematology & Oncology·Patrizia CerutiFrancesco Novelli
Apr 30, 2014·Archives of Toxicology·Márton JaniPéter Krajcsi
Jan 18, 2012·Biochemical Pharmacology·Karthika NatarajanDouglas D Ross
Aug 4, 2015·Nature Communications·Juan D ChavezJames E Bruce
Aug 1, 2014·Biochimica Et Biophysica Acta·Mafalda VideiraMaria Alexandra Brito
Nov 15, 2011·Journal of Clinical Pathology·Mark K Heatley

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