In the present study, Tbx3, a member of the T-box family of transcription factors, was identified as an up-regulated gene by mRNA differential display in the regression (apoptosis) stage after uracil-induction of papillomatosis in the rat urinary bladder. Immunohistochemical analysis revealed that apoptosis cells are negative and apoptosis resistant cells are positive for Tbx3 expression. That suggests that Tbx3 is an apoptosis resistant gene rather than an apoptosis induced gene. We have found the rat bladder carcinoma cell line, BC31, to feature Tbx3 expression detectable by RT-PCR. To investigate its role in such cancer cells, they were transfected with an anti-sense Tbx3 expression vector. The obtained stable transfectant clones showed reduced expression of Tbx3 and much slower cell growth, as compared with mock transfectants, and many apoptotic cells were observed under normal culture conditions. These results indicate that Tbx3 is a negative regulator of apoptosis in bladder normal epithelial cells and suppression of Tbx3 expression causes inhibition of cell proliferation and induction of apoptosis in BC31, a rat bladder carcinoma cells.