Effect of Cytotoxic Drugs on Estrogen Receptor Expression and Response to Tamoxifen in MCF-7 Cells1

Robert C. Clarke, Janet M. Morwood, Hendrik W. van den Berg, John N. Nelson, Richard F. Murphy

Research output: Contribution to journalArticle

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Abstract

We have examined the effects of a 24-h exposure to clinically achievable concentrations of adriamycin, melphalan, 5-fluorouracil, and vincristine on the estrogen binding capacity of MCF-7 human breast cancer cells using a whole cell binding assay. Adriamycin (0.018 to 1.8 μm),melphalan (0.1 to 5 μm),5-fluorouracil (0.077 to 15.4 μm),and vincristine (0.01 to 1 nM) reduce the estrogen binding capacity in a dose dependent manner. The rate of protein synthesis is reduced following exposure to 5-fluorouracil but not following exposure to adriamycin, melphalan, or vincristine. The rate of cell proliferation, influx of the ligand, and the Kdof remaining estrogen receptor are unaltered following drug exposure. These drugs may, therefore, be inducing a nonspecific reduction in the rate of receptor recycling and/or synthesis. Vincristine (1 nM) abolished estrogen receptor expression but following removal of the drug receptor levels did not reach that expressed in untreated cells for at least 48 h. Prior exposure to vincristine (1 nM) reduced the antiproliferative effects of tamoxifen (2 μm)toward MCF-7 cells.

Original languageEnglish (US)
Pages (from-to)6116-6119
Number of pages4
JournalCancer Research
Volume46
StatePublished - Jan 12 1986
Externally publishedYes

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    Clarke, R. C., Morwood, J. M., van den Berg, H. W., Nelson, J. N., & Murphy, R. F. (1986). Effect of Cytotoxic Drugs on Estrogen Receptor Expression and Response to Tamoxifen in MCF-7 Cells1. Cancer Research, 46, 6116-6119.