A mechanism of drug resistance to tamoxifen in breast cancer

Jennifer MacGregor Schafer, David J. Bentrem, Hiroyuki Takei, Csaba Gajdos, Sunil Badve, V. Craig Jordan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Drug resistance to tamoxifen (Tam) is a significant clinical problem but the mechanism through which this occurs remains elusive. We have developed a number of xenograft models of Tam-stimulated growth that model breast cancer progression using estrogen receptor positive MCF-7 or T47D breast cancer cells. When estrogen-stimulated T47D:E2 tumors are treated long term with Tam, Tam-stimulated tumors develop (T47D:Tam) that are stimulated by both estrogen and Tam. When HER-2/neu status is determined, it is clear that the T47D:Tam tumors express significantly higher levels of HER-2/neu protein by immunohistochemistry and mRNA as measured by real-time RT-PCR. The T47D:Tam tumors also express higher levels of estrogen receptor and progesterone receptor protein than their estrogen-stimulated T47D:E2 counterparts. We compared out results to the MCF-7 model of Tam-stimulated growth. The MCF-7:Tam ST (estrogen- and Tam-stimulated) and MCF-7:Tam LT (estrogen-inhibited, Tam-stimulated) were bilaterally transplanted to account for any mouse to mouse variation and characteristic growth patterns were observed. TUNEL staining was performed on MCF-7:Tam LT treated with either estrogen or Tam and it was concluded that estrogen-inhibited tumor growth was a result of increased apoptosis. Three phases of tumor progression are described that involve increases in HER-2/neu expression, de-regulation of estrogen receptor expression and increases in apoptosis which in concert determine the phenotype of drug resistance to Tam.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume83
Issue number1-5
DOIs
StatePublished - Dec 2002
Externally publishedYes

Fingerprint

Tamoxifen
Drug Resistance
Breast Neoplasms
Pharmaceutical Preparations
Estrogens
Tumors
Estrogen Receptors
Neoplasms
Growth
Apoptosis
Deregulation
In Situ Nick-End Labeling
Progesterone Receptors
Heterografts
Real-Time Polymerase Chain Reaction

Keywords

  • Antiestrogen
  • Breast cancer
  • Drug resistance
  • Estrogen receptor
  • HER-2/neu

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

A mechanism of drug resistance to tamoxifen in breast cancer. / Schafer, Jennifer MacGregor; Bentrem, David J.; Takei, Hiroyuki; Gajdos, Csaba; Badve, Sunil; Jordan, V. Craig.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 83, No. 1-5, 12.2002, p. 75-83.

Research output: Contribution to journalArticle

Schafer, Jennifer MacGregor ; Bentrem, David J. ; Takei, Hiroyuki ; Gajdos, Csaba ; Badve, Sunil ; Jordan, V. Craig. / A mechanism of drug resistance to tamoxifen in breast cancer. In: Journal of Steroid Biochemistry and Molecular Biology. 2002 ; Vol. 83, No. 1-5. pp. 75-83.
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