Down-regulation of ras and myc expression associated with mdr-1 overexpression in adriamycin-resistant tumor cells.
The murine melanoma tumor cells, B16-BL6, are a recognized model for experimental and spontaneous metastasis. B16-BL6 cells express a lower metastatic phenotype upon acquisition of resistance to adriamycin. Using this novel system, the role of ras, c-myc, and multidrug-resistant gene (mdr1) expression in the metastatic and drug-resistant phenotype was examined. The metastatic cells expressed a high level of c-Ki-ras and c-myc, whereas down-regulation of both proto-oncogenes was observed in the adriamycin-resistant cells. The mdr1 gene, which encodes P-glycoprotein of the drug-resistant superfamily gene, was overexpressed in drug-resistant melanoma cells. These results suggest that altered expression of genes that regulate cellular proliferation and growth may be a determinant of metastasis and drug sensitivity of tumor cells.
Department of Molecular Biology, Cleveland Clinic Foundation, OH 44195.
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Banerjee
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Ganapathi
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Ghosh
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CL
Yu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D015342:DNA Probes; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D008546:Melanoma, Experimental / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D009857:Oncogenes / Q000235:genetics*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D015342:DNA Probes; D008562:Membrane Glycoproteins; D004317:Doxorubicin