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Novel Candidate Targets of �-Catenin/T-cell Factor Signaling Identified by Gene Expression Profiling of Ovarian Endometrioid Adenocarcinomas 1

By Donald R. Schwartz, Rong Wu, Sharon L. R. Kardia, Albert M. Levin, Chiang-ching Huang, Kerby A. Shedden, Rork Kuick, David E. Misek, Samir M. Hanash, Jeremy M. G. Taylor, Heather Reed, Neali Hendrix, Yali Zhai, Eric R. Fearon and Kathleen R. Cho


The activity of �-catenin (�-cat), a key component of the Wnt signaling pathway, is deregulated in about 40 % of ovarian endometrioid adenocarcinomas (OEAs), usually as a result of CTNNB1 gene mutations. The function of �-cat in neoplastic transformation is dependent on T-cell factor (TCF) transcription factors, but specific genes activated by the interaction of �-cat with TCFs in OEAs and other cancers with Wnt pathway defects are largely unclear. As a strategy to identify �-cat/TCF transcriptional targets likely to contribute to OEA pathogenesis, we used oligonucleotide microarrays to compare gene expression in primary OEAs with mutational defects in �-cat regulation (n � 11) to OEAs with intact regulation of �-cat activity (n � 17). Both hierarchical clustering and principal component analysis based on global gene expression distinguished �-cat-defective tumors from those with intact �-cat regulation. We identified 81 potential �-cat/TCF targets by selecting genes with a

Year: 2008
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