Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line
Bruce Dickstein
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorEva M. Valverius
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorKatja Wosikowski
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorMiguel Saceda
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorJack W. Pearson
Laboratory of Experimental Immunology, Biological Response Modifiers Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorMary Beth Martin
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorCorresponding Author
Susan E. Bates
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892Search for more papers by this authorBruce Dickstein
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorEva M. Valverius
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorKatja Wosikowski
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorMiguel Saceda
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorJack W. Pearson
Laboratory of Experimental Immunology, Biological Response Modifiers Program, National Cancer Institute, Bethesda, Maryland 20892
Search for more papers by this authorMary Beth Martin
Lombardi Cancer Research Center, Georgetown University, Washington, D.C. 20007
Search for more papers by this authorCorresponding Author
Susan E. Bates
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892
Medicine Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland 20892Search for more papers by this authorAbstract
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-giycoprotein 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 × 106 sites per cell with unaltered affinity when compared to parental MCF-7 cells, which have 2.7 × 105 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. © 1993 Wiley-Liss, Inc.
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