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

George Edelstyn Laboratory, Departments of Biochemistry [R. C., J. M., J. N., and R. F. M.] and of Therapeutics and Pharmacology [H. W., v. d. B.] The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, Northern Ireland, United Kingdom BT9 7BL

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 K_d of 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.

¹ This work was supported by a grant from Action Cancer (Northern Ireland).

² To whom requests for reprints should be addressed.

Received 1/31/86. Revised 7/ 1/86. Accepted 8/14/86.