p21WAF1/cIP1 mediates the growth response to TGF-β in human epithelial cells

被引：39
|
作者：
Bachman, KE
Blair, BG
Brenner, K
Bardelli, A
Arena, S
Zhou, SB
Hicks, J
De Marzo, AM
Argani, P
Park, BH
机构：
[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
来源：
CANCER BIOLOGY & THERAPY | 2004年 / 3卷 / 02期
关键词：
p21; TGF-beta; arrest; proliferation; breast cancer;
D O I：
10.4161/cbt.3.2.666
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：221 / 225
页数：5
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