Title: Smad3 Is a Key Nonredundant Mediator of Transforming Growth Factor beta Signaling in Nme Mouse Mammary Epithelial Cells
Authors: Dzwonek-Lapinska, Joanna ×
Preobrazhenska, Olena
Cazzola, Silvia
Conidi, Andrea
Schellens, Ann
van Dinther, Maarten
Stubbs, Andrew
Klippel, Anke
Huylebroeck, Danny
ten Dijke, Peter
Verschueren, Kristin #
Issue Date: Aug-2009
Publisher: Amer assoc cancer research
Series Title: Molecular Cancer Research vol:7 issue:8 pages:1342-1353
Abstract: Smad2 and Smad3 are intracellular mediators of transforming growth factor beta (TGF beta) signaling that share various biochemical properties, but data emerging from functional analyses in several cell types indicate that these two Smad proteins may convey distinct cellular responses. Therefore, we have investigated the individual roles of Smad2 and Smad3 in mediating the cytostatic and proapoptotic effects of TGF beta as well as their function in epithelial-to-mesenchymal transition. For this purpose, we transiently depleted mouse mammary epithelial cells (Nme) of Smad2 and/or Smad3 mainly by a strategy relying on RNaseH-induced degradation of mRNA. The effect of such depletion on hallmark events of TGF beta-driven epithelial-to-mesenchymal transition was analyzed, including dissolution of epithelial junctions, formation of stress fibers and focal adhesions, activation of metalloproteinases, and transcriptional regulation of acknowledged target genes. Furthermore, we investigated the effect of Smad2 and Smad3 knockdown on the TGF beta-regulated transcriptome by microarray analysis. Our results identify Smad3 as a key factor to trigger TGF beta-regulated events and ascribe tumor suppressor as well as oncogenic activities to this protein. (Mol Cancer Res 2009;7(8):1342-53)
ISSN: 1541-7786
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Biology (Celgen) (-)
Laboratory of Behavioral and Developmental Genetics
× corresponding author
# (joint) last author

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