Format

Send to

Choose Destination
See comment in PubMed Commons below
Oncogene. 2001 Feb 15;20(7):879-84.

Smad7 inhibits the survival nuclear factor kappaB and potentiates apoptosis in epithelial cells.

Author information

1
INSERM U. 482, Hôpital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France.

Abstract

In this study, we examined the effect of the stable expression of Smad7 in two different cell lines on apoptosis induced by various stimuli including TGF-beta, serum withdrawal, loss of cell adhesion (anoikis) and TNF-alpha. Smad7 increased TGF-beta-mediated apoptosis in Mv1Lu cells as well as anoikis and/or serum withdrawal-induced apoptosis in Mv1Lu and MDCK cells. Smad7 markedly decreased the activity of the survival NF-kappaB transcription factor in MDCK cells. Interestingly, the stable expression of oncogenic Ras in MDCK cells which suppressed Smad7 inhibition of NF-kappaB also suppressed Smad7 potentiation of serum withdrawal-induced apoptosis and anoikis. In addition, Smad7 inhibited TNF-alpha stimulation of NF-kappaB and increased TNF-alpha-mediated apoptosis in MDCK cells. Our results provide the first evidence that Smad7 induces sensitization of cells to different forms of cell death. They moreover demonstrate that Smad7 inhibits the survival NF-kappaB factor, providing a potential mechanism whereby Smad7 potentiates cell death.

PMID:
11314022
DOI:
10.1038/sj.onc.1204167
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center