BioProject

TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. More...

TGF-betas have complex roles in tumorigenesis, with context-dependent effects that can either suppress or promote tumor progression. Our goal was to use integrated genomic approaches in a model of human breast cancer progression to identify core TGF-beta-regulated genes that specifically reflect the tumor suppressor activity of TGF-beta. The model consisted of the non-tumorigenic MCF10A (“M1”), the premalignant MCF10AT1k.cl2 (“M2”), the early malignant MCF10Ca1h (“M3”) and the highly malignant, metastatic MCF10Ca1a.cl1 (“M4”) cell lines. We have previously shown that tumor suppressor activity of TGF-beta is dependent on Smad3, and is lost in M4 cells. To identify how TGF-beta/Smad3 targets change with cancer progression, we performed promoter-wide Smad3 ChIP-chip on all four cell lines of the breast cancer progression model (M1-M4), following treatment with TGF-beta or vehicle control. Overall design: Subconfluent cultures of the four cell lines (M1-M4) were serum-starved for 16 h and then treated with 5ng/ml of TGF-beta1 (plus condition) or vehicle alone (minus condition) for 1hour. Smad3 ChIP was performed using the Abcam #28379 anti-Smad3 antibody. Four biological replicates were performed for each condition (plus and minus) for M1 and M2 cells, and two biological replicates for each condition for M3 and M4 cells; total of 24 samples. Less...