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Int. J. Mol. Sci. 2010, 11(9), 3039-3051; doi:10.3390/ijms11093039

Article

P-Glycoprotein/MDR1 Regulates Pokemon Gene Transcription Through p53 Expression in Human Breast Cancer Cells

Shengnan He^1,2,† , Feng Liu^1,† , Zhenhua Xie¹ , Xuyu Zu¹ , Wei Xu^2,*  and Yuyang Jiang^1,3,*

¹ The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong, China ² School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China ³ School of Medicine, Tsinghua University, Beijing 100084, Beijing, China ^† These authors contributed equally to this work.

* Authors to whom correspondence should be addressed.

Received: 16 July 2010; in revised form: 3 August 2010 / Accepted: 23 August 2010 / Published: 27 August 2010

(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

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Abstract: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter and plays an important role in pharmacokinetics. In this study, we demonstrated that the pokemon promoter activity, the pokemon mRNA and protein expression can be significantly inhibited by Pgp. Chromatin immunoprecipitation assay showed that Pgp can bind the pokemon prompter to repress pokemon transcription activity. Furthermore, Pgp regulated pokemon transcription activity through expression of p53 as seen by use of p53 siRNA transfected MCF-7 cells or p53 mutated MDA-MB-231 cells. Moreover, p53 was detected to bind with Pgp in vivo using immunoprecipitation assay. Taken together, we conclude that Pgp can regulate the expression of pokemon through the presence of p53, suggesting that Pgp is a potent regulator and may offer an effective novel target for cancer therapy.

Keywords: Pgp (MDR1); Pokemon; p53; breast cancer

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