Enhanced S100 calcium-binding protein P expression sensitizes human bladder cancer cells to cisplatin.
OBJECTIVE
• To investigate the role of S100 calcium-binding protein P (S100P) in the gain of cis-diamminedichloroplatinum (II) (cisplatin) resistance in bladder cancer, having previously found, with cDNA microarrays using two pairs of parental (T24, KK47) and their cisplatin-resistant bladder cancer cell lines (T24/DDP10, KK47/DDP20), that S100P mRNA expression was significantly reduced in cisplatin-resistant cells.


METHODS
• S100P mRNA and protein expression levels were investigated by northern and western blot analyses, respectively. • Intracellular S100P localization was examined by immunocytochemistry and immunohistochemistry. • S100P over-expression, obtained by transfection with S100P expression plasmid, was used to investigate whether or not S100P affected cellular resistance to cisplatin.


RESULTS
• S100P mRNA showed increased expression by cisplatin stimulation in parental cell lines. • On the other hand, S100P mRNA and protein expression levels were markedly reduced in cisplatin-resistant cells. • The over-expression of S100P in resistant cells resulted in an increased sensitivity to cisplatin.


CONCLUSIONS
• In bladder cancer cells, S100P was expressed and localized mainly in the nucleus. • S100P expression was also involved in cisplatin sensitivity. • S100P might thus represent a molecular marker predicting cisplatin sensitivity and a molecular therapeutic target for cisplatin-based chemotherapy.
Shiota
Masaki
M
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tsunoda
Toshiyuki
T
Song
Yoohyun
Y
Yokomizo
Akira
A
Tada
Yasuhiro
Y
Oda
Yoshinao
Y
Naito
Seiji
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C103003:S100P protein, human; D002945:Cisplatin