Effect of Disrupting Cell Contact on the Nuclear Accumulation of β-Catenin and Subsequent Apoptosis of Rat Ovarian Surface Epithelial Cells In Vitro

Abstract

The present studies were designed to determine how disrupting cell contact induces rat ovarian surface epithelial cells (i.e., ROSE-179 cells) to undergo apoptosis. In the first series of studies, the effect of depleting serum and calcium on the levels of the adhesion proteins N-cadherin and beta-catenin was examined. These studies revealed that the depletion of serum and calcium results in the degradation of N-cadherin but not beta-catenin. However, the localization of beta-catenin changed from principally the plasma membrane to the nucleus. The nuclear localization of beta-catenin was demonstrated by Western blot and confocal microscopy. A second series of studies demonstrated that cells that lost contact in response to the depletion of serum and calcium showed enhanced beta-catenin-dependent transcription. Finally, forced expression of a stable form of beta-catenin resulted in an increase in beta-catenin within the cytoplasm of transfected ROSE-179 cells. When these beta-catenin transfected ROSE-179 cells were deprived of serum and calcium, beta-catenin accumulated within the nucleus and accelerated the rate at which these cells became apoptotic. These data indicate that in viable cells, beta-catenin is part of the adhesion complex that maintains cell contact. If calcium-dependent cell contacts are broken, beta-catenin accumulates within the nucleus, where it promotes transcription and ultimately the apoptotic death of ROSE-179 cells.

Chlamydia trachomatis Disrupts N-Cadherin-Dependent Cell-Cell Junctions and Sequesters β-Catenin in Human Cervical Epithelial Cells

“…Previous studies have shown that cells infected with C. trachomatis become resistant to apoptotic stimuli (21,22). At the same time, other studies have shown that the release of ␤-catenin from junctional complexes into the cytosol may be an important step in the initiation of apoptotic death in several types of cells (3,15,20,29,46,60,62). Perhaps, by binding ␤-catenin and disrupting one of the pathways that leads to apoptotic cell death, C. trachomatis might prolong the life of the infected cell so that the organism can develop and mature.…”

Early events in ovarian epithelial carcinogenesis: progress and problems in experimental approaches

“…Interestingly, with neoplastic progression, the tendency of OSE to undergo epithelio‐mesenchymal conversion diminishes and the cells become increasingly committed to complex epithelial phenotypes which include the formation of glandular structures and papillae (1,4,13,14) . They also acquire the epithelial adhesion molecule E‐cadherin which may act as a survival factor (15–17) and increased expression of the receptor for hepatocyte growth factor ( c‐met ) which contributes to the growth and invasiveness of many forms of cancer (18) . The stability of these epithelial phenotypes under a variety of conditions in vivo and in culture most likely reflects a form of autonomy, ie, unresponsiveness to environmental controls, which is one of the hallmarks of neoplastic cells.…”

Implications of a Multi-Step Trigger of Retinal Regeneration in the Adult Newt

“…It is known that β-catenin, which associates with the intracellular domain of cadherin on the cell membrane, is released from cadherin and sends a signal to the nucleus, when cadherin-mediated cell–cell contact is disrupted by calcium depletion [15]. In the newt, RPE cells express N-cadherin ([12]; see below).…”