Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines.
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.
Tsunoda
Toshiyuki
T
Department of Urology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Koga
Hirofumi
H
Yokomizo
Akira
A
Tatsugami
Katsunori
K
Eto
Masatoshi
M
Inokuchi
Junichi
J
Hirata
Akira
A
Masuda
Katsuaki
K
Okumura
Koji
K
Naito
Seiji
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020411:Oligonucleotide Array Sequence Analysis; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D015220:Calcium Channels; D002614:Chelating Agents; D003432:Cross-Linking Reagents; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D004533:Egtazic Acid; D011065:Poly(ADP-ribose) Polymerases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002945:Cisplatin; D002118:Calcium