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Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor.

Publication ,  Journal Article
Connor, CE; Norris, JD; Broadwater, G; Willson, TM; Gottardis, MM; Dewhirst, MW; McDonnell, DP
Published in: Cancer Res
April 1, 2001

Tamoxifen inhibits estrogen receptor (ER) transcriptional activity by competitively inhibiting estradiol binding and inducing conformational changes in the receptor that may prevent its interaction with coactivators. In bone, the cardiovascular system, and some breast tumors, however, tamoxifen exhibits agonist activity, suggesting that the tamoxifen-ER complex is not recognized identically in all cells. We used phage display to demonstrate that the antiestrogen GW5638 induces a unique structural change in the ER. The biological significance of this conformational change was revealed in studies that demonstrated that tamoxifen-resistant breast tumor explants are not cross-resistant to GW5638. Because of these properties, this drug is currently being developed as a potential therapeutic for tamoxifen-resistant breast cancers.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2001

Volume

61

Issue

7

Start / End Page

2917 / 2922

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tamoxifen
  • Stilbenes
  • Receptors, Estrogen
  • Protein Conformation
  • Oncology & Carcinogenesis
  • Neoplasms, Hormone-Dependent
  • Molecular Sequence Data
  • Mice, Nude
  • Mice, Inbred BALB C
 

Citation

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MLA
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Connor, C. E., Norris, J. D., Broadwater, G., Willson, T. M., Gottardis, M. M., Dewhirst, M. W., & McDonnell, D. P. (2001). Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor. Cancer Res, 61(7), 2917–2922.
Connor, C. E., J. D. Norris, G. Broadwater, T. M. Willson, M. M. Gottardis, M. W. Dewhirst, and D. P. McDonnell. “Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor.Cancer Res 61, no. 7 (April 1, 2001): 2917–22.
Connor CE, Norris JD, Broadwater G, Willson TM, Gottardis MM, Dewhirst MW, et al. Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor. Cancer Res. 2001 Apr 1;61(7):2917–22.
Connor CE, Norris JD, Broadwater G, Willson TM, Gottardis MM, Dewhirst MW, McDonnell DP. Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor. Cancer Res. 2001 Apr 1;61(7):2917–2922.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2001

Volume

61

Issue

7

Start / End Page

2917 / 2922

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tamoxifen
  • Stilbenes
  • Receptors, Estrogen
  • Protein Conformation
  • Oncology & Carcinogenesis
  • Neoplasms, Hormone-Dependent
  • Molecular Sequence Data
  • Mice, Nude
  • Mice, Inbred BALB C