Loss of TGF-b growth inhibition is a hallmark of many human tumors. The TGF-b signaling pathway involves the activation of APC, which in turn facilitates the destruction of SnoN, a transcriptional co-suppressor, thereby mediating the transactivation of TGF-b responsive genes responsible for cell cycle arrest. APC appears to act in conjunction with other moieties, including Cdh1 and Smad2/Smad3, but the mechanism by which it is activated by TGF-b signaling is poorly understood. To elucidate the mechanism by which APC is activated by TGF-b signaling and further validate the role of TGF-b activated APC in suppressing tumor formation, we are employing a biochemical approach and using human breast tumor xenograft model in mice to analyze APC mediated TGF-b-induced tumor suppression.