1. Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line.
- Author
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Dickstein B, Valverius EM, Wosikowski K, Saceda M, Pearson JW, Martin MB, and Bates SE
- Subjects
- Animals, Cell Division drug effects, Cell Line, Drug Resistance, Epidermal Growth Factor pharmacology, ErbB Receptors genetics, Estrogens metabolism, Female, Mice, Mice, Nude, Proto-Oncogene Proteins c-fos metabolism, RNA, Messenger metabolism, Transforming Growth Factor alpha metabolism, Doxorubicin pharmacology, ErbB Receptors metabolism, Estrogens pharmacology
- Abstract
We examined the expression of the estrogen and epidermal growth factor (EGF) receptors in a drug-resistant subline of MCF-7 cells in order to study potential alterations in hormone dependence or in the growth factor pathway that could be related to the development of drug resistance in human breast cancer. The drug-resistant subline was derived from MCF-7 cells by selection with Adriamycin in the presence of the P-glycoprotein antagonist, verapamil, to prevent acquisition of the classical multidrug resistance phenotype. The Adriamycin-resistant cells retain estrogen-binding, estrogen-responsive monolayer growth, and estrogen-dependent tumorigenesis. Estrogen-binding studies demonstrate 1.4 x 10(6) sites per cell with unaltered affinity when compared to parental MCF-7 cells, which have 2.7 x 10(5) sites per cell. An increase in expression of EGF receptor, eight to 12-fold, occurred early in the selection for drug resistance, and appears to be unrelated to verapamil exposure, since cells maintained in Adriamycin without verapamil also have increased EGF receptor expression. Partially drug-sensitive revertants carried a verapamil, but out of Adriamycin, demonstrate a decline in EGF receptor expression. We postulate that activation of growth factor pathways in drug-resistant cells may enhance mechanisms of drug resistance, or provide mitogenic stimuli for cells to recover after damage by drug exposure.
- Published
- 1993
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