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

What’s known on the subject? and What does the study add? So far, several molecules have been reported to be involved in cisplatin resistance. This study revealed that a decreased expression of S100P is implicated in cisplatin resistance. In addition, S100P overexpression rendered bladder cancer cells sensitive 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. 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.