Fig 5.

TGF-β signaling is inactive in ERα-positive breast cancer cell lines because of transcriptional silencing of the TGFBR2 gene. a TGF-β treatment failed to induce Smad phosphorylation in ERαpositive human breast cancer cell lines, while ERα-negative cell lines responded to exogenous TGF-β by activating Smad2 and −3. b Expression of a 92-gene TBRS [62] in human breast cancer cell lines [33]. Using Gene Set Enrichment Analysis, a score between −1 and +1 was derived, indicating the likelihood that TGF-β signaling is active (>0) or not (<0) in individual cell lines [11]. Cell line scores within each major breast cancer subset are depicted as boxplots. Consistent with their inability to respond to TGF-β, luminal breast cancer cell lines do not express the TBRS, while it is clearly represented within the gene expression profiles of ERα-negative cell lines. c We found a striking inverse correlation between ESR1 and TGFBR2 mRNA transcript levels across our panel of 9 human breast cancer cell lines by qRT-PCR. Thus, unresponsiveness to TGF-β is apparently due to silencing of TGFBR2 gene expression. d Contour plots of ESR1 and TGFBR2 mRNA transcript levels across human breast cancer cell lines reported in three different published studies [33–35]. Strikingly, in each of the three studies, human breast cancer cell lines expressed either ESR1 or TGFBR2 mRNA but rarely both