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Estrogen- and Tamoxifen-induced Rearrangement of Cytoskeletal and Adhesion Structures in Breast Cancer MCF-7 Cells¹

Section of Pathological Anatomy and Histology, Department of Biomedical Sciences and Oncology, University of Turin, School of Medicine, Via Santena 7, 10126 Torino, Italy [A. S., F. P., G. B.] and Section of Histology and Embryology, Department of Biomedical Sciences and Oncology, University of Turin, School of Medicine, Corso M. D'Azeglio 52, 10126 Torino, Italy [P. C. M.]

The cytoskeleton, the shape, and the adhesion complexes of MCF-7 breast carcinoma cells have been studied by fluorescence, phase contrast, and interference reflection microscopy. Cells have been grown in media containing different concentrations of estrogen and with or without the addition of the antiestrogen tamoxifen. The pattern of actin microfilaments and keratin intermediate filaments (tonofilaments) and the distribution of adhesion areas change as a function of the estrogen concentration.

When cells are cultured in estrogen-deprived medium, they appear roundish and flattened and adhere firmly to the substratum, with multiple vinculin-positive adhesion plaques at their ventral surface. Upon stimulation with estrogen, these cells display pseudopodial cytoplasmic protrusions and ruffling membranes; in interference reflection microscopy the adhesion areas are mostly localized in these projections. A rearrangement of microfilaments and of tonofilaments in the cell projections and the formation of a dense network of keratin fibers takes place. Tamoxifen affects cellular shape and cytoskeletal arrangement in a way similar to that induced by estrogen.

An effect of estrogen-receptor stimulation on the adhesion structures and on the rearrangement of intermediate and actin filaments (and accordingly of the shape and internal structure of breast cancer cells) can be suggested. Such an effect might be direct or mediated through unknown mechanisms; it seems, however, to be independent of the well known estrogenic effect on cell proliferation.

¹ Supported by grants from the M.P.I., Rome, the C.N.R. Progetto Finalizzato "Oncologia" (grants n. 84.00478.44 and n. 84.00658.44), and the A.I.R.C., Milan, Italy.

² To whom requests for reprints should be addressed, at Department of Biomedical Sciences and Oncology, Section of Pathological Anatomy and Histology, University of Turin, Via Santena 7, 10126 Torino, Italy.

Received 12/ 3/84. Revised 7/ 5/85. Revised 1/ 3/86. Accepted 1/29/86.

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