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. 2004 Feb;3(2):221-5.
doi: 10.4161/cbt.3.2.666. Epub 2004 Feb 1.

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

Kurtis E Bachman  1 , Brian G Blair, Keith Brenner, Alberto Bardelli, Sabrina Arena, Shibin Zhou, Jessica Hicks, Angelo M De Marzo, Pedram Argani, Ben Ho Park
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Free article

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

Kurtis E Bachman et al. Cancer Biol Ther. 2004 Feb.
Free article

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.

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