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Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines

Oncogene volume 24, pages 1396–1402 (2005)Cite this article

Abstract

To investigate the molecules that regulate the acquisition of cis-diamminedichloroplatinum (II) (cisplatin) resistance, we performed cDNA microarrays using two pairs of parental and cisplatin-resistant bladder cancer cell lines. We found a markedly reduced expression of inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1), endoplasmic reticulum membrane protein, in cisplatin-resistant cells. The suppression of IP3R1 expression using small interfering RNA in parental cells prevented apoptosis and resulted in decreased sensitivity to cisplatin. Contrarily, overexpression of IP3R1 in resistant cells induced apoptosis and increased sensitivity to cisplatin. These results suggest that cisplatin-induced downregulation of IP3R1 expression was closely associated with the acquisition of cisplatin resistance in bladder cancer cells.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (C), No. 14571506, 2002 from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We are grateful to Dr TC Sudhof, Director of the Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, and Dr M Iino, Director of the Department of Pharmacology, Graduate School of Medicine, University of Tokyo, Japan, who donated the pCDNA3-IP3R1 mammalian expression vector. We also thank M Matsuda for expert advice; N Hakoda, M Yamada, T Kuramachi, and H Matoba for technical assistance; and B Quinn and KM Rudiger for help in preparing the manuscript.

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  1. Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Toshiyuki Tsunoda, Hirofumi Koga, Akira Yokomizo, Katsunori Tatsugami, Masatoshi Eto, Junichi Inokuchi, Akira Hirata, Katsuaki Masuda, Koji Okumura & Seiji Naito

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  1. Toshiyuki Tsunoda
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  2. Hirofumi Koga
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  4. Katsunori Tatsugami
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Correspondence to Seiji Naito.

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Tsunoda, T., Koga, H., Yokomizo, A. et al. Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines. Oncogene 24, 1396–1402 (2005). https://doi.org/10.1038/sj.onc.1208313

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