Unexpected Lower Expression of Oncoprotein Gankyrin in Drug Resistant ABCG2 Overexpressing Breast Cancer Cell Lines

Abstract

Background:Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin(p28, p28GANKor PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/MX) and non-MDR counterparts (MCF-7).Methods:Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2(also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR. Western blot analysis was used to detect the protein expression levels of Gankyrin.Results:The PCR results showed that the expression of Gankyrin was significantly lower in the ABCG2overexpressing cell line MCF-7/MX than in non-resistanct MCF-7 cells. In contrast, there were no significant differences in mRNA expression of Gankyrin in the MDR1 overexpressing cell line MCF-7/ADR in comparison with MCF-7 cells. Similarly, Western blot analysis confirmed lower expression of Gankyrin protein in the MCF-7/MX cell line (26% compared to controls) but not in MCF-7/ADR cells.Conclusion:These findings showed that there may be a relation between down-regulation of Gankyrin and overexpression of ABCG2 but without any clear relationship with MDR1 expression in breast cancer cell lines.