p21WAF1/CIP1 mediates the growth response to TGF-β in human epithelial cells

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

doi:10.4161/cbt.3.2.666

p21^WAF1/CIP1 mediates the growth response to TGF-β in human epithelial cells

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

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

We investigated the mechanism by which cancers evade the growth inhibitory effects of TGF-β. Using two p21^-/- somatically deleted human epithelial cell lines, we find that TGF-β serves as a growth stimulator rather than a growth suppressor to cells lacking p21. In addition, TGF-β stimulated p2^-/- 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.

Original language	English (US)
Pages (from-to)	221-225
Number of pages	5
Journal	Cancer Biology and Therapy
Volume	3
Issue number	2
DOIs	https://doi.org/10.4161/cbt.3.2.666
State	Published - Feb 2004

Keywords

Arrest
Breast cancer
Proliferation
TGF-β
p21

ASJC Scopus subject areas

Molecular Medicine
Oncology
Pharmacology
Cancer Research

Access to Document

10.4161/cbt.3.2.666

Cite this

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title = "p21WAF1/CIP1 mediates the growth response to TGF-β in human epithelial cells",

abstract = "We investigated the mechanism by which cancers evade the growth inhibitory effects of TGF-β. Using two p21-/- somatically deleted human epithelial cell lines, we find that TGF-β serves as a growth stimulator rather than a growth suppressor to cells lacking p21. In addition, TGF-β stimulated p2-/- 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.",

keywords = "Arrest, Breast cancer, Proliferation, TGF-β, p21",

author = "Bachman, {Kurtis E.} and Blair, {Brian G.} and Keith Brenner and Alberto Bardelli and Sabrina Arena and Shibin Zhou and Jessica Hicks and {De Marzo}, {Angelo M.} and Pedram Argani and Ben, {Ho Park}",

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AU - Bachman, Kurtis E.

AU - Blair, Brian G.

AU - Brenner, Keith

AU - Bardelli, Alberto

AU - Arena, Sabrina

AU - Zhou, Shibin

AU - Hicks, Jessica

AU - De Marzo, Angelo M.

AU - Argani, Pedram

AU - Ben, Ho Park

PY - 2004/2

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AB - We investigated the mechanism by which cancers evade the growth inhibitory effects of TGF-β. Using two p21-/- somatically deleted human epithelial cell lines, we find that TGF-β serves as a growth stimulator rather than a growth suppressor to cells lacking p21. In addition, TGF-β stimulated p2-/- 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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KW - Proliferation

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KW - p21

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