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Breast Cancer Research and Treatment

, Volume 31, Issue 1, pp 129–138 | Cite as

The estrogen receptor from a tamoxifen stimulated MCF-7 tumor variant contains a point mutation in the ligand binding domain

  • Douglas M. Wolf
  • V. Craig Jordan
Article

Abstract

The nonsteroidal antiestrogen tamoxifen (TAM) is the most commonly used endocrine treatment for all stages of breast cancer in both pre- and postmenopausal women. However, the development of resistance to the drug is common, as most patients treated with TAM eventually experience a recurrence of tumor growth. One of the potential mechanisms of treatment failure is the acquisition by the tumor of the ability to respond to TAM as a stimulatory rather than inhibitory ligand. We (Gottardis and Jordan, Cancer Res 48: 5183-5187, 1988; Wolfet al., J Natl Cancer Inst 85: 806-812, 1993) and others (Osborneet al., Eur J Cancer Clin Oncol 23: 1189-1196, 1987; Osborneet al., J Natl Cancer Inst 83: 1477-1482, 1991) have extensively described the reproducible development of TAM stimulated growth in a laboratory model system using MCF-7 human breast cancer cells grown as solid tumors in athymic mice. In this paper we report on the isolation of an estrogen receptor (ER) from a TAM stimulated tumor (MCF-7/MT2) which contains a point mutation that causes a tyrosine for aspartate substitution at amino acid 351 in the ligand binding domain. The mutant appears to the major form of ER expressed by this tumor. We also report that only wild type ER was detected in three other TAM stimulated MCF-7 tumor variants, suggesting that multiple mechanisms are possible for the development of TAM stimulated growth. The implications of these findings are discussed.

Key words

breast cancer tamoxifen drug resistance estrogen receptor mutant 

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Douglas M. Wolf
    • 1
  • V. Craig Jordan
    • 2
  1. 1.Department of Human OncologyUniversity of Wisconsin Comprehensive Cancer CenterMadisonUSA
  2. 2.Department of PharmacologyUniversity of Wisconsin Comprehensive Cancer CenterMadisonUSA

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