Differential expression of estrogen receptor mRNA splice variants in the tamoxifen resistant human breast cancer cell line, MCF-7/TAMR-1 compared to the parental MCF-7 cell line

Madsen, M.W.; Reiter, B.E.; Lykkesfeldt, A.E.

Molecular and Cellular Endocrinology 109(2): 197-207

1995


ISSN/ISBN: 0303-7207
PMID: 7664983
DOI: 10.1016/0303-7207(95)03503-y
Accession: 008472132

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Abstract
Breast cancer patients with an estrogen receptor (ER) positive tumor can be treated with the anti-estrogen tamoxifen, but development of anti-estrogen resistance is a serious problem. We have analyzed a tamoxifen resistant human breast cancer cell line MCF-7/TAM-R-1 for alterations in ER which might explain the tamoxifen resistance. The MCF-7/TAM-R-1 cells expressed both wildtype ER mRNA and protein, and by RT-PCR we were able to clone ER cDNAs corresponding to the following mRNA splice variants: ER-DELTA-E2, ER-DELTA-E4, ER-DELTA-E5, ER-DELTA-E7 and a new double splice variant lacking both exon 4 and 7 (ER-DELTA-E4,7). The existence of the ER-DELTA-E4,7 variant was confirmed by RNase protection assay. Semi-quantitative RT-PCR revealed that ER-DELTA-E2 mRNA was expressed at a higher level in MCF-7/TAM-R-1 cells, whereas the ER-DELTA-E5 mRNA was expressed at a significantly lower level in MCF-7/TAM-R-1 cells compared with MCF-7 cells. The differential expression of the two ER mRNA splice variants indicates that they may be involved in anti-estrogen resistance, although the present knowledge of their biological function does not provide us with an explanation.