Therefore, studies were undertaken to examine a role for TGFβ signaling in ER+ osteolytic BMET progression using a variety of in vivo human ER+ osteolytic breast cancer xenograft models, including an assessment of tumoral Smad-mediated TGFβ signaling and possible crosstalk in bone tropic ER+ breast cancer cells between osteolytic TGFβ and E2 signaling pathways. The gene discussed is TGFB1; the disease is breast cancer.