Transcriptional Regulation of Breast Cancer Resistance Protein (BCRP) by p53 in p53-null Saos-2 cells

WU Xin-Gang*, PENG Shu-Bin, LV Si-Ping, ZHANG Nian-Feng, ZOU Jin

Chinese Journal of Biochemistry and Molecular Biology ›› 2012, Vol. 28 ›› Issue (2) : 152-157.

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Chinese Journal of Biochemistry and Molecular Biology ›› 2012, Vol. 28 ›› Issue (2) : 152-157.
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Transcriptional Regulation of Breast Cancer Resistance Protein (BCRP) by p53 in p53-null Saos-2 cells

  • WU Xin-Gang*,  PENG Shu-Bin,  LV Si-Ping,  ZHANG Nian-Feng, ZOU Jin
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Abstract

Breast cancer resistance protein (BCRP) is a member of the ATP-binding cassette (ABC) transporter superfamily. BCRP confers drug resistance in cancer by transporting chemotherapeutic agents such as mitoxantrone, topotecan, and methotrexate. Although a recent study demonstrated that wild type p53 (wt-p53) may suppress BCRP expression through the nuclear factor-κB (NF-κB) pathway in breast cancer cell line MCF-7, which expresses wt-p53 at low level, the detailed molecular mechanisms of transcriptional regulation on BCRP remain unclear. Here, we set out to reveal the exogenous p53's role on the expression of BCRP. In the human osteosarcoma cell line Saos-2, a p53-null cell line, transient transfection assays showed that the BCRP expression was activated by wt-p53 but not p53 mutants,p53R175H and p53R248W. We further co-transfected the p53 expression plasmid with BCRP luciferase promoter reporter construct into the Saos-2 cell, and the results revealed that wt-p53 may facilitate the BCRP promoter activity. However, we did not find any p53 binding site by applying MatInspector. Strikingly, NF-κB activity inhibition downplayed the activation effect of BCRP promoter activity by wt-p53.These results suggested that transcriptional activation of BCRP by wt-p53 is NF-κB- dependent.

Key words

breast cancer resistance protein (BCRP) / p53 / nuclear factor-κB (NF-κB)

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WU Xin-Gang*, PENG Shu-Bin, LV Si-Ping, ZHANG Nian-Feng, ZOU Jin . Transcriptional Regulation of Breast Cancer Resistance Protein (BCRP) by p53 in p53-null Saos-2 cells[J]. Chinese Journal of Biochemistry and Molecular Biology, 2012, 28(2): 152-157

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Funding

Supported by Yueyang Higher Vocational and Technical College (No.YZ1104G)

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