Tumor Suppressor Pten Inhibits Nuclear Accumulation of β-Catenin and T Cell/Lymphoid Enhancer Factor 1–Mediated Transcriptional Activation

DOI PDF 被引用文献2件
  • Sujata Persad
    aBritish Columbia Cancer Agency, Jack Bell Research Center, Vancouver V6H 3Z6, British Columbia, Canada
  • Armelle A.Troussard
    aBritish Columbia Cancer Agency, Jack Bell Research Center, Vancouver V6H 3Z6, British Columbia, Canada
  • Timothy R. McPhee
    aBritish Columbia Cancer Agency, Jack Bell Research Center, Vancouver V6H 3Z6, British Columbia, Canada
  • David J. Mulholland
    bThe Prostate Centre at Vancouver General Hospital, Jack Bell Research Center, Vancouver V6H 3Z6, British Columbia, Canada
  • Shoukat Dedhar
    aBritish Columbia Cancer Agency, Jack Bell Research Center, Vancouver V6H 3Z6, British Columbia, Canada

書誌事項

公開日
2001-06-04
DOI
  • 10.1083/jcb.153.6.1161
公開者
Rockefeller University Press

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<jats:p>β-Catenin is a protein that plays a role in intercellular adhesion as well as in the regulation of gene expression. The latter role of β-catenin is associated with its oncogenic properties due to the loss of expression or inactivation of the tumor suppressor adenomatous polyposis coli (APC) or mutations in β-catenin itself. We now demonstrate that another tumor suppressor, PTEN, is also involved in the regulation of nuclear β-catenin accumulation and T cell factor (TCF) transcriptional activation in an APC-independent manner. We show that nuclear β-catenin expression is constitutively elevated in PTEN null cells and this elevated expression is reduced upon reexpression of PTEN. TCF promoter/luciferase reporter assays and gel mobility shift analysis demonstrate that PTEN also suppresses TCF transcriptional activity. Furthermore, the constitutively elevated expression of cyclin D1, a β-catenin/TCF–regulated gene, is also suppressed upon reexpression of PTEN. Mechanistically, PTEN increases the phosphorylation of β-catenin and enhances its rate of degradation. We define a pathway that involves mainly integrin-linked kinase and glycogen synthase kinase 3 in the PTEN-dependent regulation of β-catenin stability, nuclear β-catenin expression, and transcriptional activity. Our data indicate that β-catenin/TCF–mediated gene transcription is regulated by PTEN, and this may represent a key mechanism by which PTEN suppresses tumor progression.</jats:p>

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