EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity

Ming Lu, Kathy Miller, Yesim Polar, Meei Huey Jeng, Michael S. Kinch

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The EphA2 receptor tyrosine kinase is found at low levels on nontransformed adult breast epithelial cells but is frequently overexpressed on aggressive breast cancer cells. Recent studies have documented an inverse relationship between EphA2 and estrogen receptor expression in breast cancer cell lines. In our present study, we demonstrate that overexpression of EphA2 decreases estrogen dependence as defined using both in vitro and in vivo criteria. The EphA2-transfected cells demonstrate increased growth in vitro and form larger and more aggressive tumors in vivo. EphA2 overexpression also decreases the ability of tamoxifen to inhibit breast cancer cell growth and tumorigenesis. These effects of EphA2 overexpression can be overcome by antibody-based targeting of EphA2. In particular, certain EphA2 antibodies can resensitize EphA2-overexpressing breast tumor cells to tamoxifen. These results have important implications for understanding the molecular basis underlying estrogen dependence and provide further evidence that EphA2 may provide a much-needed therapeutic target for breast cancer.

Original languageEnglish
Pages (from-to)3425-3429
Number of pages5
JournalCancer Research
Volume63
Issue number12
StatePublished - Jun 15 2003

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Tamoxifen
Estrogens
Breast Neoplasms
EphA2 Receptor
Antibodies
Growth
Estrogen Receptors
Carcinogenesis
Breast
Epithelial Cells
Cell Line
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity. / Lu, Ming; Miller, Kathy; Polar, Yesim; Jeng, Meei Huey; Kinch, Michael S.

In: Cancer Research, Vol. 63, No. 12, 15.06.2003, p. 3425-3429.

Research output: Contribution to journalArticle

Lu, Ming ; Miller, Kathy ; Polar, Yesim ; Jeng, Meei Huey ; Kinch, Michael S. / EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity. In: Cancer Research. 2003 ; Vol. 63, No. 12. pp. 3425-3429.
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