Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro

D. J. Scott, A. T. Parkes, F. Ponchel, M. Cummings, I. Poola, V. Speirs*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Tamoxifen resistance (TAMr) in breast cancer is a serious clinical dilemma, with no satisfactory explanation. We hypothesised that changes in the expression of steroid hormone receptors (ERα, ERβ), their downstream target genes (PR, pS2) and their associated co-regulators (AIB-1, SRC-1, SRA, NCoR-1, SMRT and REA) could be related to the acquisition of TAMr. To test this hypothesis, we developed in vitro TAMr cell line models by continuous exposure of MCF-7 cells to 4-hydroxytamoxifen (4-HT) over 12 (MCF-7MMU1) and 21 (MCF-7MMU2) months, respectively and examined the expression of the above by Western blotting and immunohistochemistry. In addition, we further examined the changes in global gene expression in TAMr cells in comparison with TAM-sensitive cells by microarray analysis. We report here that acquisition of TAMr is associated with changes in the expression of PR, pS2 and several co-activators, but not ERs. In addition, genes associated with cell cycle, cell adhesion and extracellular matrix, were up-regulated while those associated with apoptosis or growth factors/hormones were down-regulated. Based on our results, it appears that increased co-activator expression, in concert with alterations in genes associated with controlling cell proliferation and survival contribute to TAMr in breast cancer.

Original languageEnglish
Pages (from-to)557-565
Number of pages9
JournalInternational Journal of Oncology
Volume31
Issue number3
DOIs
Publication statusPublished - Sep 2007

Fingerprint

Steroid Receptors
Tamoxifen
Genes
Tissue Array Analysis
Breast Neoplasms
MCF-7 Cells
Cell Adhesion
Growth Hormone
Extracellular Matrix
In Vitro Techniques
Cell Survival
Intercellular Signaling Peptides and Proteins
Cell Cycle
Western Blotting
Immunohistochemistry
Cell Proliferation
Hormones
Apoptosis
Gene Expression
Cell Line

Keywords

  • Breast cancer
  • Microarray
  • Tamoxifen resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro. / Scott, D. J.; Parkes, A. T.; Ponchel, F.; Cummings, M.; Poola, I.; Speirs, V.

In: International Journal of Oncology, Vol. 31, No. 3, 09.2007, p. 557-565.

Research output: Contribution to journalArticle

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