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 differentiation in vitro when treated with 17-beta-estradiol. A prominent feature of this process is the postconfluent development of multicellular, three-dimensional nodules that rise above the surrounding monolayer. Formation of the nodules suggests that changes in cellular adhesion occur during this cellular overgrowth. Therefore changes in the distribution of cell-matrix and cell-cell adhesion plaque proteins were examined with respect to estradiol induction of nodule development. Estradiol treatment of the carcinoma cell line had the following effects: (1) vinculin- and talin-rich cell-matrix adhesion plaques were reduced 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 reduced in cell-cell adhesions situated at the apical region of subconfluent, confluent and postconfluent monolayers. Staining for F-actin and plakoglobin 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 observed. In addition, in untreated monolayer cells, both F-actin and plakoglobin were concentrated in a subapical/basolateral location, as a vesicle-like pattern, which corresponded to intercellular spaces observed with phase-contrast microscopy. Treatment with estradiol caused the rearrangement of subapical/basolateral F-actin and plakoglobin staining into a more uniform pattern. The findings of this study show that estradiol induces changes in both cell-matrix and cell-cell adhesions in an estrogen-responsive carcinoma cell line. The gradual loss of vinculin from cell-matrix and cell-cell adherens junctions of the monolayer could be a potential factor in the capacity of these cells to form multilayers or nodules in postconfluent growth. Furthermore, the development of the nodules in response to estradiol may provide a useful system in which to study steroid hormone regulation of adhesion and the cytoskeleton in responsive tumor cells.
DePasquale
J A
JA
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Samsonoff
W A
WA
Gierthy
J F
JF
D000199:Actins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000648:ultrastructure*; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000648:ultrastructure*; D016608:Talin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016596:Vinculin / Q000378:metabolism; D051185:gamma Catenin
D000199:Actins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D016608:Talin; D051185:gamma Catenin; D016596:Vinculin; D004958:Estradiol