Loss of p73 induction in a cisplatin-resistant bladder cancer cell line

Background: Cisplatin (CDDP) plays an important role in the treatment of tr ansitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood. Methods: To assess acquired resistance to CDDP, we established a CDDP-resis tant subclone, CL8-2, of T24, which is a bladder cancer cell line, We exami ned the changes in the various pathways leading to apoptosis in the parent line and CL8-2, Results: The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL 8-2 cells were 6.4 times more resistant to CDDP than was T24, In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high l evels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activati on of caspases 3, 8, and 9, This phenomenon was not observed in CL8-2 cells . Conclusion: These results suggest that loss of p73 induction may lead to CD DP resistance of TCC.