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Sci. STKE, 26 August 2003
Vol. 2003, Issue 197, p. tw333
[DOI: 10.1126/stke.2003.197.tw333]

EDITORS' CHOICE

CELL ADHESION Bcl-2 Breaks Up Cell-Cell Junctions

Expression of Bcl-2 is stimulated by estrogen, and estrogen-responsive human tumors often have increased Bcl-2 levels. Li et al. examined the effect of overexpression of Bcl-2 on MCF-7 breast carcinoma cells and Madin-Darby canine kidney (MDCK) cells, a polarized epithelial cell line, and observed loss of cell-cell junctions and redistribution of proteins that were associated with E-cadherin-containing junctions in wild-type cells. E-cadherin, like Bcl-2, is regulated by estrogen; however, no consensus estrogen-responsive elements appear to exist in the promoter, so the regulation may be indirect. E-cadherin-containing junctions include tight junctions, gap junctions, and desmosomes. In MCF-7 cells overexpressing Bcl-2, proteins--which in wild-type cells were associated with the cell-cell junctions--were redistributed either to the cytosol or, for ZO-1, to the cytosol and the nucleus. ZO-1 is known to interact with ZONAB (ZO-1-associated nucleic acid binding protein), which stimulates expression of the epidermal growth factor receptor gene ErbB2, and indeed ErbB2 protein was increased in the Bcl-2-overexpressing cells. Upon estrogen withdrawal, wild-type MCF-7 cells dissociated from each other and became motile and also exhibited increased cell death. In contrast, the MCF-7 cells overexpressing Bcl-2 required prolonged withdrawal of estrogen in order to observe decreased Bcl-2 expression in subpopulations of cells that also formed cell-cell junctions and exhibited membrane association of the junctional proteins and cell surface expression of E-cadherin. In MDCK cells overexpressing Bcl-2, the junctional proteins were also redistributed to the cytosol; however, ZO-1 colocalized with Bcl-2 instead of appearing in the nucleus as in the MCF-7 cells. Disruption of tight junctions in the MDCK and MCF-7 cells overexpressing Bcl-2 was confirmed by a decrease in transepithelial cell resistance. Increased expression of Bcl-2 may contribute to cancer invasiveness through its role in regulating cell-cell contact, as well as contribute to the proliferation of cancer cells through its ability to inhibit apoptosis.

L. Li, J. Backer, A. S. K. Wong, E. L. Schwanke, B. F. Stewart, M. Pasdar, Bcl-2 expression decreases cadherin-mediated cell-cell adhesion. J. Cell Sci. 116, 3687-3700 (2003). [Abstract] [Full Text]

Citation: Bcl-2 Breaks Up Cell-Cell Junctions. Sci. STKE 2003, tw333 (2003).



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