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

  • Authors:
    • D. J. Scott
    • A. T. Parkes
    • F. Ponchel
    • M. Cummings
    • I. Poola
    • V. Speirs
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/ijo.31.3.557
  • Pages: 557-565
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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.

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September 2007
Volume 31 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Scott DJ, Parkes AT, Ponchel F, Cummings M, Poola I and Speirs V: Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro. Int J Oncol 31: 557-565, 2007
APA
Scott, D.J., Parkes, A.T., Ponchel, F., Cummings, M., Poola, I., & Speirs, V. (2007). Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro. International Journal of Oncology, 31, 557-565. https://doi.org/10.3892/ijo.31.3.557
MLA
Scott, D. J., Parkes, A. T., Ponchel, F., Cummings, M., Poola, I., Speirs, V."Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro". International Journal of Oncology 31.3 (2007): 557-565.
Chicago
Scott, D. J., Parkes, A. T., Ponchel, F., Cummings, M., Poola, I., Speirs, V."Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro". International Journal of Oncology 31, no. 3 (2007): 557-565. https://doi.org/10.3892/ijo.31.3.557