ESTROGEN-RECEPTOR MESSENGER-RNA SPLICE VARIANTS ARE NOT INVOLVED IN ANTIESTROGEN RESISTANCE IN SUBLINES OF MCF-7 HUMAN BREAST-CANCER CELLS

Development of resistance to tamoxifen is a serious problem in treatme nt of breast cancer patients, Although the mechanisms for development of resistance are unclear, an altered expression of alternatively spli ced estrogen receptor (ER) mRNA has been suggested to be involved. We have looked for differential expression of ER splice variants lacking exon 2 (ER Delta E2), exon 3 (ER Delta E3), exon 4 (ER Delta E4), exon 5 (ER Delta E5), exon 7 (ER Delta E7), and exons 4 and 7 (ER Delta E4 , 7) in the human breast cancer cell line MCF-7 and 10 ER-positive MCF -7 sublines resistant to the antiestrogens tamoxifen, ICI 161,384 or I CI 182,780. No major differences in the expression were demonstrated b etween MCF-7 cells and resistant cells, indicating that ER splice vari ants are not involved in antiestrogen resistance in this model system, Furthermore, despite a high mRNA level of some of the ER splice varia nts, no corresponding proteins could be detected using Western blot an alysis.