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

Mol Cell Endocrinol. 1995 Apr 1;109(2):197-207. doi: 10.1016/0303-7207(95)03503-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA, Neoplasm / genetics
  • Drug Resistance
  • Exons / genetics
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Polymerase Chain Reaction
  • RNA Splicing*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics*
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured


  • DNA, Complementary
  • DNA, Neoplasm
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Tamoxifen