Enhanced S100 calcium-binding protein P expression sensitizes human bladder cancer cells to cisplatin.

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Shiota M, Tsunoda T, Song Y, Yokomizo A, Tada Y, Oda Y, Naito S

Enhanced S100 calcium-binding protein P expression sensitizes human bladder cancer cells to cisplatin.

BJU Int. 2011 Apr;107(7):1148-53. doi: 10.1111/j.1464-410X.2010.09535.x. Epub 2010 Aug 19.

PubMed ID

20726978 [ View in PubMed

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Abstract

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. MATERIALS AND 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.