We describe that the oxidative stress reagent H2O2 increases the TGF-β-induced association between BRCA1 and Smad3 in vivo and that inactivation of BRCA1 of loss of BRCA1 sensitizes phospho-Smad3 protein to oxidative stress resulting in nuclear export of phospho-Smad3 protein, and decreased Smad3-Smad4 mediated interaction induced by TGF-β and transcriptional activation in breast cancer cells. The gene discussed is SMAD3; the disease is breast carcinoma.