Positive influence of AP-2α transcription factor on cadherin gene expression and differentiation of the ocular surface.

Autor: West-Mays, J. A., Sivak, J. M., Papagiotas, S. S., Kim, J., Nottoli, T., Williams, T., Fini, M. E.
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Zdroj: Differentiation; Apr2003, Vol. 71 Issue 3, p206-216, 11p
Abstrakt: Abstract The family of transcription factors Activating protein-2 (AP-2) are known to play important roles in numerous developmental events, including those associated with differentiation of stratified epithelia. However, to date, the influence of the AP-2 genes on endogenous gene expression in the stratified epithelia and how this affects differentiation has not been well defined. The following study examines the detailed expression of the AP-2α and AP-2β proteins in the stratified epithelia of the ocular surface, including that in the cornea and developing eyelids. The effect of altered levels of the AP-2α gene on ocular surface differentiation was also examined using a corneal epithelial cell line and AP-2α chimeric mice. Immunolocalization studies revealed that, while AP-2β was broadly expressed throughout all cell layers of the stratified corneal epithelium, AP-2α expression was confined to cell compartments more basally located. AP-2α was also highly expressed in the less differentiated cell layers of the eyelid epidermis. Overexpression of the AP-2α gene in the corneal cell line, SIRC, resulted in a dramatic change in cell phenotype including a clumping growth behavior that was distinct from the smooth monolayer of the parent cell line. Accompanying this change was an up-regulation in levels of the cell adhesion molecule, N-cadherin. Examination of the ocular surface of AP-2α chimeric mice, derived from a mixed population of AP-2α-/- and AP-2α +/+ , revealed that a down-regulation in E-cadherin expression is correlated with location of the AP-2α -/- null cells. Together, these findings demonstrate that AP-2α participates in regulating differentiation of the ocular surface through induction in cadherin expression. [ABSTRACT FROM AUTHOR]
Databáze: Supplemental Index
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