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.
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/TAMR-1 for alterations in ER which might explain the tamoxifen resistance. The MCF-7/TAMR-1 cells expressed both wild-type 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/TAMR-1 cells, whereas the ER delta E5 mRNA was expressed at a significantly lower level in MCF-7/TAMR-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.
Madsen
M W
MW
Department of Tumor Endocrinology, Danish Cancer Society, Copenhagen.
Reiter
B E
BE
Lykkesfeldt
A E
AE
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance; D005091:Exons / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen