Smad7 mediates apoptosis induced by transforming growth factor beta in prostatic carcinoma cells

Transforming growth factor beta (TGF-beta) is an important regulator of apo ptosis in some cell types, but the underlying molecular mechanisms are larg ely unknown, TGF-beta signals through type I and type II receptors and down stream effector proteins, termed Smads. TGF-beta induces the phosphorylatio n of Smad2 and Smads (receptor-activated Smads) which associate with Smad4 and translocate to the nucleus, where they regulate gene transcription [1], Smad7 protein is induced by TGF-beta 1 and has been classified as an inhib itory Smad. Smad7 prevents phosphorylation of receptor-activated Smads, the reby inhibiting TGF-beta induced signaling responses [1]. Smad7 expression is increased in rat prostatic epithelial cells undergoing apoptosis as a re sult of castration [2]. Here we have shown that TGF-beta 1 treatment or ect opic expression of Smad7 in human prostatic carcinoma cells (PC-3U) induces apoptosis. Furthermore, TGF-beta 1-induced apoptosis was prevented by inhi bition of Smad7 expression, by antisense mRNA in stably transfected cell li nes or upon transient transfection with antisense oligonucleotides in sever al investigated cell lines. These findings provide evidence for a new effec tor function for Smad7 in TGF-beta 1 signaling.