Aberrant expression of a β-catenin gain-of-function mutant induces hyperplastic transformation in the mouse cornea
Journal
Journal of Cell Science
Journal Volume
123
Journal Issue
8
Pages
1285-1294
Date Issued
2010
Author(s)
Zhang Y.
Call M.K.
Yeh L.-K.
Liu H.
Kochel T.
Chu P.-H.
Taketo M.M.
Jester J.V.
Kao W.W.-Y.
Liu C.-Y.
Abstract
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. ? 2010. Published by The Company of Biologists Ltd.
Subjects
β-catenin; Corneal epithelium; OSSN; Tumorigenesis
SDGs
Other Subjects
angiopoietin; beta catenin; cytokeratin 10; cytokeratin 12; cytokeratin 15; cytokeratin 4; laminin; matrilysin; transcription factor PAX6; uvomorulin; vasculotropin A; vasculotropin receptor 1; animal experiment; article; carcinogenesis; cell differentiation; cell proliferation; controlled study; cornea neovascularization; cornea tumor; down regulation; gene mutation; mouse; nonhuman; ocular surface squamous neoplasia; priority journal; protein expression; protein function; protein transport; upregulation; Aging; Animals; Basement Membrane; beta Catenin; Cadherins; Cell Differentiation; Cell Membrane; Cell Nucleus; Cell Proliferation; Cell Transformation, Neoplastic; Cornea; Down-Regulation; Epithelium, Corneal; Eye Neoplasms; Humans; Hyperplasia; Matrix Metalloproteinase 7; Mice; Models, Biological; Mutant Proteins; Neoplasms, Squamous Cell; Protein Transport; Up-Regulation; Murinae
Type
journal article