Mouse Model of Human Ovarian Endometrioid Adenocarcinoma Based on Somatic Defects in the Wnt/β-Catenin and PI3K/Pten Signaling Pathways
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- 作者：Rong Wu ; Neali Hendrix-Lucas ; Rork Kuick ; Yali Zhai ; Donald R. Schwartz ; Aytekin Akyol ; Samir Hanash ; David E. Misek ; Hidetaka Katabuchi ; Bart O. Williams ; Eric R. Fearon ; Kathleen ; R. Cho
- 关键词：CELLCYCLE
- 刊名：Cancer Cell
- 出版年：2007
- 出版时间：10 April 2007
- 年：2007
- 卷：11
- 期：4
- 页码：321-333
- 全文大小：1498 K
文摘
One histologic subtype of ovarian carcinoma, ovarian endometrioid adenocarcinoma (OEA), frequently harbors mutations that constitutively activate Wnt/β-catenin-dependent signaling. We now show that defects in the PI3K/Pten and Wnt/β-catenin signaling pathways often occur together in a subset of human OEAs, suggesting their cooperation during OEA pathogenesis. Deregulation of these two pathways in the murine ovarian surface epithelium by conditional inactivation of the Pten and Apc tumor suppressor genes results in the formation of adenocarcinomas morphologically similar to human OEAs with 100 % penetrance, short latency, and rapid progression to metastatic disease in upwards of 75 % of mice. The biological behavior and gene expression patterns of the murine cancers resemble those of human OEAs with defects in the Wnt/β-catenin and PI3K/Pten pathways.