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Effect of Estradiol on the Ultrastructure of the MCF₇ Human Breast Cancer Cells in Culture¹

U 148, Institut National de le Sante et de la Recherche Medicale, 60 Rue de Navacelles [F. V., D. D., H. R.], and Laboratoire Histologie, Faculté de Médecine [P. V.], 34100 Montpellier, France

We have analyzed the effect of estradiol and of two classes of antiestrogens on the morphology of the MCF₇ human breast cancer cell line by scanning and transmission electron microscopy. Estradiol progressively increased the number and the length of microvilli at the cell surface. The density of the microvilli network increased between 2 and 11 days of estrogen treatment, while the cells became more globular and less tightly attached to the surface of the dish.

Estradiol also progressively transformed cells into secretory cells containing, at Day 2, large, clear mitochondria and, at Day 4, rough endoplasmic reticulum and Golgi complexes. At Day 6, secretory granules (diameter, 0.2 µm), which mainly contained glycoproteins, were first observed in the cytoplasm. By Day 8, they were concentrated at the cell membrane and being liberated into the medium. Larger granules (diameter, 0.8 µm), which probably contained lipids, were observed later (Day 11). Cell cultures in 10% fetal calf serum not treated by charcoal contained secretory granules.

The modifications were induced by physiological concentrations of estradiol but not 5-dihydrotestosterone. Progesterone (10 nM for 8 days) completely inhibited the effect of estradiol on the microvilli and secretory activity. Tamoxifen or hydroxytamoxifen did not induce secretory activity but did alter the cell morphology compared to control cells. The effects of estradiol were observed in other estrogen receptor-positive breast cancer cell lines (ZR 75-1, T 47 D) but not in an estrogen receptornegative cell line (BT 20).

This morphological evidence that estrogens modify the cell surface of breast cancer cells in culture and transform them into "secretory cells" complements evidence that they induce the release of a glycoprotein with a molecular weight of 50,000 into the culture medium (Cell, 20: 352–362, 1980). (The molecular weight was found first to be 46,000. It seems to be closer to 52,000 in a 10% polyacrylamide gel and by using the NEN-labeled proteins as molecular weight markers.)

¹ This investigation was supported by Institut National de la Sante et de la Recherche Medicale (CRL 79-5-235-4 and PRC 118016), the Unité d'Enseignement et de Recherche of Médecine, the Fondation pour la Recherche Médicale Française, and the Association pour le Développement de la Recherche sur le Cancer.

² To whom requests for reprints should be addressed.

Received 5/13/81. Accepted 11/ 5/81.

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