Expression of P-Glycoprotein mRNA in Human Gastric Tumors

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Abstract
We have isolated a cDNA clone, pCA12-2, from a .lambda. gt11 cDNA library of an adriamycin-resistant subline of human myelogenous leukemia K562 (K562/ADM) by plaque hybridization with the 2.6 kb genomic probe of P-glycoprotein reported previously. The cDNA pCA12-2 was identified as the 3''-part of P-glycoprotein cDNA by dideoxy sequencing. By using the cDNA probe, expression of P-glycoprotein mRNA was examined in human gastric xenograft lines transplanted in nude mice and clinical samples of human gastric normal tissues and tumors. Five gastric tumor xenograft lines expressed low but significant levels of P-glycoprotein mRNA. The extent of expression was higher in some cases than that observed for R1-3, a weakly drug-resistant subline of K562. Normal gastric tissues from three patients expressed similar levels of P-glycoprotein mRNA and the extent of expression was slightly higher than that of R1-3. Two of three gastric tumor samples expressed higher levels of mRNA than normal gastric tissues. These results suggest that the intrinsic insensitivity of human gastric cancers to chemotherapy could be partly explained by the expression of P-glycoprotein.