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J. Cell Sci. 116 (18): 3687-3700


Research Article

Bcl-2 expression decreases cadherin-mediated cell-cell adhesion

Laiji Li, Jody Backer, Annisa S. K. Wong, Erin L. Schwanke, Brian G. Stewart, and Manijeh Pasdar*

Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G2H7, Canada

* Author for correspondence (e-mail: mpasdar{at}ualberta.ca)

Accepted for publication 1 May 2003.

Abstract: Bcl-2, a member of the apoptosis-regulating family of proteins confers a survival advantage on cells by inhibiting apoptosis. Bcl-2 expression is estrogen-responsive and high in various tumors. Overexpression of Bcl-2 has been associated with the loss of contact inhibition, unregulated growth and foci formation in culture.

In this study, we have examined the effects of bcl-2 overexpression and expression on cell-cell adhesion in MCF-7 and MDCK epithelial cell lines respectively. Overexpression of Bcl-2 in estrogen receptor-positive MCF-7 mammary carcinoma cells led to decreased cell surface E-cadherin and the disruption of junctional complexes concurrent with intracellular redistribution of their components. Particularly noticeable, was the partial nuclear localization of the tight junction-associated protein ZO-1 which coincided with upregulation of ErbB2. The expression of this EGF co-receptor is regulated by the ZO-1-associated transcription factor ZONAB. Growth in estrogen-depleted media led to downregulation of Bcl-2 expression and upregulation and membrane localization of all junctional proteins. Similar disruption in junctions, accompanied by decreased transepithelial resistance, was observed when Bcl-2 was expressed in MDCK cells.

These results strongly suggest that Bcl-2 expression decreases the level of functional E-cadherin thereby interfering with junction formation. The inhibition of junction formation decreases cell-cell adhesion leading to the loss of contact inhibition, which, in vivo, can lead to unregulated growth and tumorigenesis.

Key Words: E-cadherin • Catenin • Bcl-2 • Junction • Cell-cell adhesion


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