Original Paper
Oncogene (2005) 24, 1396–1402. doi:10.1038/sj.onc.1208313 Published online 20 December 2004
Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines
Toshiyuki Tsunoda1, Hirofumi Koga1, Akira Yokomizo1, Katsunori Tatsugami1, Masatoshi Eto1, Junichi Inokuchi1, Akira Hirata1, Katsuaki Masuda1, Koji Okumura1 and Seiji Naito1
1Department of Urology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Correspondence: S Naito, E-mail: naito@uro.med.Kyushu-u.ac.jp
Received 23 March 2004; Revised 10 September 2004; Accepted 20 October 2004; Published online 20 December 2004.
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.
Keywords:
cisplatin resistance, IP3R1, apoptosis, bladder cancer
