Decreased P-glycoprotein in a tamoxifen-tolerant breast carcinoma model.
The initial benefits of antiestrogen treatment in mammary cancer tend to decrease with time as antiestrogen resistant subpopulations of cancer cells predominate. The role of P-glycoprotein in this phenomenon is not known. In the tumour model investigated, estradiol increased this efflux pump, while prolonged Tamoxifen exposure resulted in cell populations tolerant to the drug and with decreased P-glycoprotein expression. While Tamoxifen resistance is clinically undesirable, selective pressure by this drug may result in cancer cell lines with increased vulnerability to other chemotherapeutic modalities.
Clinical Biochemistry, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
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Kellen
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George
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Ling
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000737:chemistry*; D000818:Animals; D004361:Drug Tolerance; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D013629:Tamoxifen / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D013629:Tamoxifen; D004958:Estradiol