17-BETA-ESTRADIOL INDUCED ALTERATIONS OF CELL-MATRIX AND INTERCELLULAR ADHESIONS IN A HUMAN MAMMARY-CARCINOMA CELL-LINE

The MCF-7 human mammary carcinoma cell line undergoes morphological di fferentiation in vitro when treated with 17-beta-estradiol. A prominen t feature of this process is the postconfluent development of multicel lular, three-dimensional nodules that rise above the surrounding monol ayer. Formation of the nodules suggests that changes in cellular adhes ion occur during this cellular overgrowth. Therefore changes in the di stribution of cell-matrix and cell-cell adhesion plaque proteins were examined with respect to estradiol induction of nodule development. Es tradiol treatment of the carcinoma cell line had the following effects : (1) vinculin- and talin-rich cell-matrix adhesion plaques were reduc ed in overall number and size in confluent and postconfluent cultures. No overt change in distribution or morphology of adhesion plaques was observed in subconfluent cultures. (2) Staining for vinculin was redu ced in cell-cell adhesions situated at the apical region of subconflue nt, confluent and postconflueut monolayers. Staining for F-actin and p lakoglobin was retained at this region in estradiol-induced cells. (3) vinculin was not detected in intercellular adhesions of nodule cells although intense labelling for both F-actin and plakoglobin was observ ed. In addition, in untreated monolayer cells, both F-actin and plakog lobin were concentrated in a subapical/basolateral location, as a vesi cle-like pattern, which corresponded to intercellular spaces observed with phase-contrast microscopy. Treatment with estradiol caused the re arrangement of subapical/basolateral F-actin and plakoglobin staining into a more uniform pattern. The findings of this study show that estr adiol induces changes in both cell-matrix and cell-cell adhesions in a n estrogen-responsive carcinoma cell line. The gradual loss of vinculi n from cell-matrix and cell-cell adherens junctions of the monolayer c ould be a potential factor in the capacity of these cells to form mult ilayers or nodules in postconfluent growth. Furthermore, the developme nt of the nodules in response to estradiol may provide a useful system in which to study steroid hormone regulation of adhesion and the cyto skeleton in responsive tumor cells.