Activity of tamoxifen and its metabolites on endocrine-dependent and endocrine-independent breast cancer cells

D. Coradini, V. Cappelletti, G. Granata, G. Di Fronzo

Research output: Contribution to journalArticlepeer-review

Abstract

To better understand the mechanism of action of antiestrogens, the growth- inhibitory effect of tamoxifen and its main metabolites N-desmethyltamoxifen and 4- hydroxytamoxifen, was studied in 6 breast cancer cell lines characterized by different steroid receptor contents. On the basis of the results, our cell lines could be classified into three groups; a first group, including 734B and ZR-75.1 cell lines, characterized by a clear endocrine-dependent behavior, in which cells were sensitive to antiestrogens although to different degrees; a second group, including MDA-MB 231 and BT20 cell lines, characterized by a clear endocrine-insensitive behavior, in which cells were affected only by the highest (10-6M) antiestrogen concentration; a thirdgroup, including MCF7 and T47D cell lines, characterized by a peculiar behavior. The T47D cell line displayed an increased growth rate after treatment with all three antiestrogens considered. Despite the positive receptor content in the MCF7 cell line, only 4-hydroxytamoxifen showed a clear antiestrogen dose-dependent effect, whereas tamoxifen decreased the cell growth rate only at lower concentrations (10-8 and 10-7 M). These results and the well-known heterogeneity of human breast tumors explain the failure of antiestrogen treatment in a certainpercentage of patients with breast cancer with a positive estrogen receptor status.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalTumor Biology
Volume12
Issue number3
DOIs
Publication statusPublished - 1991

Keywords

  • Antiestrogens
  • Breast cancer cell lines

ASJC Scopus subject areas

  • Cancer Research

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