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

被引：40

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

页码：221 / 225

页数：5

共 33 条

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