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Estrogen Receptors in Human Myeloma Cells¹

Department of Hygiene [T. O., H.T S., A. U.] and Division of Hematology Departments of Internal Medicine [O. Y., K. Y., Y. Y.], Breast and Thyroid Surgery [J. K., H. K.], and Radiation Oncology [M. U.], Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan, and Department of Pathology, Tohoku University Hospital, Miyagi 980-8574, Japan [T. M.]

It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-, ER-ß, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated. In addition, effects on membrane Fas expression, appearance of apoptosis, and cell cycle perturbation were analyzed. It was revealed that ER-ß and corepressors were dominantly expressed in myeloma cells, and antiestrogens induced growth inhibition through apoptosis mediated by a Fas-related pathway and G₁ arrest of the cell cycle in myeloma cell lines.

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