Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways

被引：287

作者：

Wu, Rong

Hendrix-Lucas, Neali

Kuick, Rork

Zhai, Yali

Schwartz, Donald R.

Akyol, Aytekin

Hanash, Samir

Misek, David E.

Katabuchi, Hidetaka

Williams, Bart O.

Fearon, Eric R.

Cho, Kathleen R. ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA

[7] Kumamoto Univ, Fac Med & Pharmaceut Sci, Dept Gynecol, Kumamoto 8608556, Japan

[8] Van Andel Res Inst, Grand Rapids, MI 49503 USA

来源：

CANCER CELL | 2007年 / 11卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2007.02.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

One histologic subtype of ovarian carcinoma, ovarian endonnetrioid adenocarcinorna (OEA), frequently harbors mutations that constitutively activate Wnt/beta-catenin-dependent signaling. We now show that defects in the PI3K/Pten and Wnt/beta-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/beta-catenin and PI3K/Pten pathways.

引用

页码：321 / 333

页数：13

共 65 条

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