SMAD2 and breast cancer: Specifically, reduction in SMAD2/3 signaling by ectopic expression of ALK5RImL45/T204D enhanced the malignancy of xenografted tumors of the well-differentiated MCF10A-derived BC cell line, MCF10CA1h, resulting in formation of larger tumors with a higher proliferative index and more malignant histologic features (50).