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Estrogen Receptor Messenger RNA Splice Variants Are Not Involved in Antiestrogen Resistance in Sublines of MCF-7 Human Breast Cancer Cells¹

Department of Tumor Endocrinology, Division for Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark

Development of resistance to tamoxifen is a serious problem in treatment of breast cancer patients. Although the mechanisms for development of resistance are unclear, an altered expression of alternatively spliced estrogen receptor (ER) mRNA has been suggested to be involved. We have looked for differential expression of ER splice variants lacking exon 2 (ERE2), exon 3 (ERE3), exon 4 (ERE4), exon 5 (ERE5), exon 7 (ERE7), and exons 4 and 7 (ERE4, 7) in the human breast cancer cell line MCF-7 and 10 ER-positive MCF-7 sublines resistant to the antiestrogens tamoxifen, ICI 164,384 or ICI 182,780. No major differences in the expression were demonstrated between MCF-7 cells and resistant cells, indicating that ER splice variants are not involved in antiestrogen resistance in this model system. Furthermore, despite a high mRNA level of some of the ER splice variants, no corresponding proteins could be detected using Western blot analysis.

¹ This work was supported by the Danish Cancer Society and by Mogens Ambt Balslev's Memorial Foundation.

² To whom requests for reprints should be addressed.

Received 8/29/96. Accepted 1/ 3/97.

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