Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor

Abstract.

We report the isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein. A λgt11 cDNA library derived from colorectal carcinoma SW480 cells was screened with monoclonal antibody MGr1. DNA homology analysis of 22 positive clones (designated R1–R22) suggested human 37-kDa laminin receptor precursor (37LRP, R7/R9/R15/R16/R19/R20) and a novel gene (R22) as candidate genes encoding MGr1-Ag. Western blot analysis showed that anti-R20 serum reacted with a unique protein band that was consistent with MGr1-Ag, while anti-R22 serum could not react with MGr1-Ag. The coding gene for MGr1-Ag was amplified using reverse transcription-PCR. Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence. An in vitro drug sensitivity assay indicated that down-regulation of 37LRP by an antisense technique could significantly enhance the cytotoxicity of anticancer drugs to gastric cancer cells. Thus we draw the conclusion that MGr1-Ag is identical to 37LRP.