Aberrant expression of a β-catenin gain-of-function mutant induces hyperplastic transformation in the mouse cornea

Yujin Zhang, Mindy K. Call, Lung Kun Yeh, Hongshan Liu, Tyler Kochel, I. Jong Wang, Pao Hsien Chu, Makoto M. Taketo, James V. Jester, Winston W.Y. Kao, Chia Yang Liu*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

23 引文 斯高帕斯(Scopus)

摘要

β-catenin signaling has been shown to play a fundamental role in embryonic development and tumorigenesis. In this study, we investigated the role of β-catenin (Ctnnb1) in corneal homeostasis and tumorigenesis. Conditional expression of a murine Ctnnb1 gain-of-function mutation alone caused corneal neoplasia and neovascularization, resembling human ocular surface squamous neoplasia (OSSN). These corneas displayed an upregulation of cell proliferative markers (PCNA and p63), while presenting downregulation of both the Pax-6 transcription factor and the corneal differentiation marker cytokeratin 12. In addition, the expression of limbal-type keratin 15 ectopically extended to cornea, but the pattern of conjunctival keratin 4 and epidermal keratin 10 were unchanged. Moreover, epithelial E-cadherin and laminins decreased concomitantly with elevated levels of MMP-7. We also noticed a dramatic upregulation of pro-angiogenic factors (Vegf-A, Vegfr1) and angiopoietins in these corneas. Interestingly, all human OSSN specimens examined revealed nuclear β-catenin immunoreactivity. Taken together, these results argue that β-catenin activation is a crucial step during OSSN pathogenesis. Thus, inhibition of β-catenin might be beneficial for treating this disease.

原文英語
頁(從 - 到)1285-1294
頁數10
期刊Journal of Cell Science
123
發行號8
DOIs
出版狀態已出版 - 15 04 2010
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