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Cancer Biol Ther. 2004 Feb;3(2):221-5. Epub 2004 Feb 1.

p21(WAF1/CIP1) mediates the growth response to TGF-beta in human epithelial cells.

Author information

1
The Sidney Kimmel Comprehensive Canter Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, Maryland 21231, USA.

Abstract

We investigated the mechanism by which cancers evade the growth inhibitory effects of TGF-beta. Using two p21-/- somatically deleted human epithelial cell lines, we find that TGF-beta serves as a growth stimulator rather than a growth suppressor to cells lacking p21. In addition, TGF-beta stimulated p21-/- cells exhibited a mesenchymal phenotype, demonstrated by an upregulation of vimentin and decreased expression of E-cadherin. Analysis of primary human breast cancers by immunohistochemical labeling confirmed a correlation between p21 loss and positive vimentin expression. These data provide a molecular mechanism explaining how nongastrointestinal cancers can escape the anti-proliferative effects of this cytokine and simultaneously use this pathway for growth advantage.

PMID:
14726675
DOI:
10.4161/cbt.3.2.666
[Indexed for MEDLINE]

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