Non-Nuclear Role of the Estrogen Receptor Alpha in the Regulation of Cell-Cell Interactions.

摘要

Proliferation and metastasis of many breast cancers depend on the activity of estrogen receptors (ERs). In addition to regulating nuclear gene expression, ERalpha can act in association with the plasma membrane. In vitro interaction studies by our laboratory led the hypothesis that membrane- localized ERalpha might weaken cell adhesions by impeding alpha/beta catenin heterodimerization, which is necessary for the formation of stable adherens junctions. To test this hypothesis we constructed MCF7 lines that over express ER variants known to alter ERalpha membrane location, and monitored the composition of adherens junctions in these cells. Consistent with a role of membrane-associated ERalpha in cell adhesion, these lines displayed distinct adhesion properties. However, we did not detect direct interactions of ERalpha with adherens junctions or ERalpha dependent changes in the composition of adherens junctions. In contrast to our hypothesis, membrane-associated ERalpha appeard to enhance cell adhesions. Interaction studies revealed that ERalpha preferentially interacts with alpha-catenin homo-dimers with the Arp2/3 complex resulting in changes in the actin polymerization. Analysis of MCF7 lines supported estrogen induced changes in actin polymerization in the vicinity of the membrane. These results suggest that membrane-localized ER indeed play a role in the formation of cell adhesions, however likely through another mechanism as originally hypothesized.