Increased expression of T-plastin gene in cisplatin-resistant human cancer cells: identification by mRNA differential display.

The cellular resistance to the potent anticancer agent cis-diamminedichloroplatinum(II) (cisplatin) is thought to be mediated by multiple mechanisms. The technique of differential display of mRNAs was applied to various cisplatin-resistant cell lines and the corresponding parental sensitive human bladder, prostatic, and head and neck cancer cells in order to identify genes that underlie cisplatin resistance. Twenty-four clones were confirmed by Northern blot analysis to be expressed differentially between resistant and the corresponding sensitive cells. Partial DNA sequences of the eight clones that showed a threefold or greater increase in expression in either the resistant cells (seven clones) or sensitive cells (one clone) revealed that two were derived from the T-plastin gene and one from the tissue factor gene. The abundance of T-plastin mRNA in cisplatin-resistant T24/DDP10 cell was approximately 12 times that in the parental T24 cells. Transfection of T24/DDP10 cells with a vector encoding full-length T-plastin antisense RNA demonstrated that reduced T-plastin expression was associated with increased sensitivity to cisplatin. These results are consistent with the hypothesis that several mechanisms participate cooperatively in the acquisition of cisplatin resistance in human cancer.