H19 GENE OVEREXPRESSION IN ATYPICAL MULTIDRUG-RESISTANT CELLS ASSOCIATED WITH EXPRESSION OF A 95-KILODALTON MEMBRANE GLYCOPROTEIN

The multidrug resistance phenotype of human breast carcinoma MCF-7/Adr Vp cells is characterized by overexpression of a 95-kilodalton membran e glycoprotein (p95), accompanied by a marked reduction in intracellul ar anthracycline accumulation, without overexpression of P-glycoprotei n or the multidrug resistance protein. We discovered that the mRNA of the H19 gene is overexpressed in MCF-7/AdrVp cells relative to parenta l MCF-7 cells or drug-sensitive MCF-7/AdrVp revertant cells, H19 is an imprinted gene with an important role in fetal differentiation, as we ll as a postulated function as a tumor suppressor gene. Another p95-ov er-expressing multidrug-resistant cell line, human lung carcinoma NCI- H1688, also displays high levels of H19 mRNA. In contrast, several mul tidrug-resistant cell lines that overexpress P-glycoprotein or the mul tidrug resistance protein do not have higher levels of H19 mRNA than t heir drug-sensitive counterparts. This is the first report of H19 gene overexpression accompanying any form of drug resistance. The associat ion of H19 and p95 gene expression in drug resistance warrants further study.