Cellular resistance to adriamycin conferred by enhanced Rb expression is associated with increased MDR1 expression.
In order to investigate if the enhanced expression of Rb confers increased cellular resistance to adriamycin, we made Rb stable transfectants from colon carcinoma cells, SW620. Rb stable transfectants exhibited 5- to 10-fold more resistance to adriamycin than the control cells. To study the correlation between enhanced Rb expression and MDR1 expression, products of the Rb gene and the MDR1 gene in Rb stable transfectants were measured by Western blot analysis. These Rb transfectants showed increased MDR1 expression. Transient transfection of the MDR1 promoter-CAT reporter gene and the Rb gene demonstrated that Rb up-regulated MDR1 promoter activity in SW620 cells. Rb may, at least partly, contribute to a role in protecting cells from carcinogen exposure by up-regulating the MDR1 gene.
Laboratory of Experimental Therapeutics, Korea Cancer Center Hospital, Seoul, Korea. ydy@kcchsun.kcch.re.kr
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016160:Retinoblastoma Protein / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D016160:Retinoblastoma Protein; D004317:Doxorubicin