Molecular Characterization of Tgf Mediated Cancer Cell Proliferation (Paperback)

TGF 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 TGF switch from a cell cycle inhibitor to a growth promoter pathway in cancer cells. TGF induces the expression and activation of NFAT factors, which then translocate into the nucleus to promote c-Myc expression. In response to TGF, 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 TGF -promoted cell growth that is defined by sequential transcriptional activation of NFAT and c-Myc factors.

General

Imprint:	VDM Verlag
Country of origin:	Germany
Release date:	November 2010
First published:	November 2010
Authors:	Garima Singh • Shiv Kishor Singh • Volker Ellenrieder
Dimensions:	229 x 152 x 6mm (L x W x T)
Format:	Paperback - Trade
Pages:	100
ISBN-13:	978-3-639-29801-7
Categories:	Books > Science & Mathematics > Biology, life sciences > General
LSN:	3-639-29801-2
Barcode:	9783639298017

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