| Molecular Characterization of Tgf Mediated Cancer Cell Proliferation Contributor(s): Singh, Garima (Author), Singh, Shiv Kishor (Author), Volker Ellenrieder (Author) |
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ISBN: 3639298012 ISBN-13: 9783639298017 Publisher: VDM Verlag OUR PRICE: $50.27 Product Type: Paperback Published: November 2010 |
| Additional Information |
| BISAC Categories: - Science | Life Sciences - Biology |
| Physical Information: 0.24" H x 6" W x 9" (0.35 lbs) 100 pages |
| Descriptions, Reviews, Etc. |
| Publisher Description: TGFβ has a dual role in carcinogenesis, acting as a growth inhibitor in early tumor stages and a promoter of cell proliferation in advanced diseases. Although this cellular phenomenon is well established, the underlying molecular mechanisms remain elusive. Here, we report that sequential induction of NFAT and c-Myc transcription factors is sufficient and required for the TGFβ switch from a cell cycle inhibitor to a growth promoter pathway in cancer cells. TGFβ induces the expression and activation of NFAT factors, which then translocate into the nucleus to promote c-Myc expression. In response to TGFβ, activated NFAT factors bind to and displace Smad3 repressor complexes from the c-Myc promoter. c-Myc in turn stimulates cell cycle progression and growth through up-regulation of D-type cyclins. Most importantly, NFAT knockdown not only prevents c-Myc activation and cell proliferation, but also partially restores TGF-beta-induced cell cycle arrest and growth suppression. Taken together, this study provides the first evidence for a Smad-independent master regulatory pathway in TGFβ-promoted cell growth that is defined by sequential transcriptional activation of NFAT and c-Myc factors. |