Because TGFβ did not alter ER phosphorylation, a mechanism by which some growth factors after nuclear ER signaling [42], it is possible that additive effects of E2 and TGFβ on secretion of PTHrP, an osteolytic factor overexpressed in breast cancer BMETs vs. other metastatic sites [17,18] with similar overexpression here in ER+ BMET-derived cells, could simply be attributable to separate, but additive effects of canonical Smad-mediated TGFβRII and ER signaling (i.e., induction of gene expression by activated nuclear Smads and ERα). The gene discussed is TGFB1; the disease is breast cancer.