p21 (WAF1/CIP1) Mediates the Growth Response to TGF-b in Human Epithelial Cells

作者：Kurtis E. Bachman, Brian G. Blair, KEITH R BRENNER, Alberto Bardelli, Sabrina Arena, Shibin Zhou, Jessica L Hicks, Angelo M. De Marzo, Pedram Argani, Ben Ho Park · 发表于：Cancer Biology & Therapy · 年份：2004 · DOI：10.4161/cbt.3.2.666 · 被引用次数：45 · 研究领域：TGF-β signaling in diseases、Cancer-related Molecular Pathways、Fibroblast Growth Factor Research

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.