Title of article :
ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with β-catenin defects and promotes neoplastic transformation
Author/Authors :
Kolligs، نويسنده , , Frank T. and Nieman، نويسنده , , Marvin T. and Winer، نويسنده , , Ira and Hu، نويسنده , , Gang and Van Mater، نويسنده , , David and Feng، نويسنده , , Ying and Smith، نويسنده , , Ian M. and Wu، نويسنده , , Rong and Zhai، نويسنده , , Yali and Cho، نويسنده , , Kathleen R. and Fearon، نويسنده , , Eric R.، نويسنده ,
Abstract :
In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in β-catenin lead to elevated β-catenin levels, enhanced binding of β-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by β-catenin or ligand-induced activation of a β-catenin-estrogen receptor fusion protein. Human cancers with β-catenin regulatory defects had elevated ITF-2 expression, and ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note, ITF-2 promoted neoplastic transformation of RK3E cells. We propose that ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in β-catenin regulation.
