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

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

doi:10.1038/sj.onc.1208313

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

Oncogene. 2005 Feb 17;24(8):1396-402. doi: 10.1038/sj.onc.1208313.

Authors

Toshiyuki Tsunoda¹, Hirofumi Koga, Akira Yokomizo, Katsunori Tatsugami, Masatoshi Eto, Junichi Inokuchi, Akira Hirata, Katsuaki Masuda, Koji Okumura, Seiji Naito

Affiliation

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

PMID: 15608674
DOI: 10.1038/sj.onc.1208313

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / physiology
Calcium / physiology
Calcium Channels / genetics
Calcium Channels / physiology*
Cell Line, Tumor
Chelating Agents / pharmacology
Cisplatin / pharmacology*
Cross-Linking Reagents / pharmacology
Down-Regulation / genetics
Drug Resistance, Neoplasm / genetics
Egtazic Acid / analogs & derivatives*
Egtazic Acid / pharmacology
Gene Expression Profiling
Gene Expression Regulation, Neoplastic / drug effects
Humans
Inositol 1,4,5-Trisphosphate Receptors
Oligonucleotide Array Sequence Analysis
Poly(ADP-ribose) Polymerases / physiology
RNA, Small Interfering / genetics
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / physiology*
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*

Substances

Antineoplastic Agents
Calcium Channels
Chelating Agents
Cross-Linking Reagents
ITPR1 protein, human
Inositol 1,4,5-Trisphosphate Receptors
RNA, Small Interfering
Receptors, Cytoplasmic and Nuclear
Egtazic Acid
Poly(ADP-ribose) Polymerases
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Cisplatin
Calcium