Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes.
作者： S I Hsu , L Lothstein , S B Horwitz
DOI: 10.1016/S0021-9258(18)80173-9
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摘要: Abstract A hallmark of the multidrug-resistant phenotype is overproduction a family 130-180-kDa integral membrane phosphoglycoproteins collectively called P-glycoprotein. Gene-specific hybridization probes were derived from three classes mouse P-glycoprotein cDNAs. These revealed differential amplification and/or transcriptional activation distinct but closely related mdr genes (mdr1a, mdr1b, and mdr2) in independently selected J774.2 cell lines. Overexpression mdr1a mdr1b was found to correlate, general, with either 120- or 125-kDa precursor, respectively. This same correlation observed single line during course stepwise selection for resistance vinblastine which switch gene expression resulted 125- 120-kDa precursor. findings suggest that overexpression encode unique isoforms possible mechanism generating diversity phenotype.
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