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Figure 2 | Molecular Cancer

Figure 2

From: Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

Figure 2

Effects of TGF-β antagonists on Smad activation in MDA-MB-231-derived metastatic subclones. A. Cells were starved in serum free DMEM medium overnight and incubated with vehicle or TGF-β antagonist for 15 minutes. Subsequently, TGF-β (100 pM) was added, and cells were incubated for an additional hour. The levels of phosphorylated Smad-2,-3 and -1/5/8 were determined by Western blotting. Induction of Smad-2 and -3 phosphorylation by exogenous TGF-β was effectively inhibited by either LY2109761 (2 μM) or 1D11 (10 μg/ml) in all six subclones. TGF-β induced Smad1 and -5 phosphorylation most strongly in the most metastatic bone-tropic (SCP2TR) and lung-tropic (4175TR and 4173) subclones, and to a lesser extent in the 2860TR and 3847TR cells. Activation of these BMP Smads was also inhibited by both antagonists. B. To assess the ability of TGF-β antagonists to induce dephosphorylation of R-Smads, bone-tropic SCP2TR cells were treated with TGF-β for 1.5 h, followed by treatment with the antagonists for the indicated time-periods. The receptor kinase inhibitor, LY2109761, induced dephosphorylation of activated Smad-2 and -3 more rapidly than the pan- TGF-β neutralizing antibody, 1D11.

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