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Smad7 inhibits the survival nuclear factor κB and potentiates apoptosis in epithelial cells
- Source :
- Oncogene. 20:879-884
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
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.
- Subjects :
- Cancer Research
Programmed cell death
Apoptosis
Biology
Culture Media, Serum-Free
Smad7 Protein
Dogs
Transforming Growth Factor beta
Genetics
Animals
Anoikis
Cell adhesion
Molecular Biology
Transcription factor
integumentary system
Tumor Necrosis Factor-alpha
NF-kappa B
Epithelial Cells
DNA-Binding Proteins
Cell culture
Trans-Activators
ras Proteins
Cancer research
Tumor necrosis factor alpha
Signal transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....a822be79d9b9e71724fec723e973673a