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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)221-225
Number of pages5
JournalCancer Biology and Therapy
Volume3
Issue number2
DOIs
StatePublished - Feb 2004

Keywords

  • Arrest
  • Breast cancer
  • Proliferation
  • TGF-β
  • p21

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'p21<sup>WAF1/CIP1</sup> mediates the growth response to TGF-β in human epithelial cells'. Together they form a unique fingerprint.

  • Cite this

    Bachman, K. E., Blair, B. G., Brenner, K., Bardelli, A., Arena, S., Zhou, S., Hicks, J., De Marzo, A. M., Argani, P., & Ben, H. P. (2004). p21WAF1/CIP1 mediates the growth response to TGF-β in human epithelial cells. Cancer Biology and Therapy, 3(2), 221-225. https://doi.org/10.4161/cbt.3.2.666