JCB logo
BioLegend: Antibody Reagents
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online February 26, 2007
doi:10.1083/jcb.200612129
The Journal of Cell Biology, Vol. 176, No. 5, 695-707
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Niimi et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Niimi, H.
Right arrow Articles by Moustakas, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Niimi, H.
Right arrow Articles by Moustakas, A.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
*Genetics Home Reference
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Notch signaling is necessary for epithelial growth arrest by TGF-ß

Hideki Niimi, Katerina Pardali, Michael Vanlandewijck, Carl-Henrik Heldin, and Aristidis Moustakas

Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE-751 24 Uppsala, Sweden

Correspondence to Aristidis Moustakas: aris.moustakas{at}licr.uu.se

Transforming growth factor ß (TGF-ß) and Notch act as tumor suppressors by inhibiting epithelial cell proliferation. TGF-ß additionally promotes tumor invasiveness and metastasis, whereas Notch supports oncogenic growth. We demonstrate that TGF-ß and ectopic Notch1 receptor cooperatively arrest epithelial growth, whereas endogenous Notch signaling was found to be required for TGF-ß to elicit cytostasis. Transcriptomic analysis after blocking endogenous Notch signaling uncovered several genes, including Notch pathway components and cell cycle and apoptosis factors, whose regulation by TGF-ß requires an active Notch pathway. A prominent gene coregulated by the two pathways is the cell cycle inhibitor p21. Both transcriptional induction of the Notch ligand Jagged1 by TGF-ß and endogenous levels of the Notch effector CSL contribute to p21 induction and epithelial cytostasis. Cooperative inhibition of cell proliferation by TGF-ß and Notch is lost in human mammary cells in which the p21 gene has been knocked out. We establish an intimate involvement of Notch signaling in the epithelial cytostatic response to TGF-ß.

H. Niimi and K. Pardali contributed equally to this paper.

H. Niimi's present address is Toyama University Faculty of Medicine, Dept. of Clinical and Molecular Pathology, Toyama City 930-0194, Japan.

K. Pardali's present address is Molecular Medicine, Dept. of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.

Abbreviations used in this paper: GAPDH, glyceraldehyde-3'-phosphate dehydrogenase; GSI, {gamma}-secretase inhibitor; HMEC, human mammary epithelial cell; MOI, multiplicity of infection; N1ICD, Notch1 intracellular domain.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents