The common denominators between Smad3 and TMEPAI deficient cells are high Smad2 transcriptional activity and low TMEPAI expression, which resulted in reduced cell growth In contrast, high Smad3 transcriptional activity combined with high TMEPAI expression promoted breast cancer cell proliferation suggesting that Smad3 may function through TMEPAI. This evidence concerns the gene SMAD2 and breast cancer.