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)

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

Bcl-2 Overexpression Induces a Partial Epithelial to Mesenchymal Transition and Promotes Squamous Carcinoma Cell Invasion and Metastasis.

J. Zuo, T. Ishikawa, S. Boutros, Z. Xiao, J. O. Humtsoe, and R. H. Kramer (2010)
Mol. Cancer Res. 8, 170-182
 |  Abstract »  |  Full Text »  |  PDF »

Lack of Bax Prevents Influenza A Virus-Induced Apoptosis and Causes Diminished Viral Replication.

J. E. McLean, E. Datan, D. Matassov, and Z. F. Zakeri (2009)
J. Virol. 83, 8233-8246
 |  Abstract »  |  Full Text »  |  PDF »

Oncogenic K-Ras Regulates Proliferation and Cell Junctions in Lung Epithelial Cells through Induction of Cyclooxygenase-2 and Activation of Metalloproteinase-9.

X.-Q. Wang, H. Li, V. Van Putten, R. A. Winn, L. E. Heasley, and R. A. Nemenoff (2009)
Mol. Biol. Cell 20, 791-800
 |  Abstract »  |  Full Text »  |  PDF »

Relationship of p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancers with comedonecrosis as an accelerated apoptosis.

N Hosaka, T Ryu, W Cui, Q Li, A Nishida, T Miyake, T Takaki, M Inaba, and S Ikehara (2006)
J. Clin. Pathol. 59, 692-698
 |  Abstract »  |  Full Text »  |  PDF »

WT1-interacting protein and ZO-1 translocate into podocyte nuclei after puromycin aminonucleoside treatment.

M. Rico, A. Mukherjee, M. Konieczkowski, L. A. Bruggeman, R. T. Miller, S. Khan, J. R. Schelling, and J. R. Sedor (2005)
Am J Physiol Renal Physiol 289, F431-F441
 |  Abstract »  |  Full Text »  |  PDF »