Frequent coordinated overexpression of the MRP/GS-X pump and γ- glutamylcysteine synthetase genes in human colorectal cancers

We have recently shown that multidrug resistance-associated protein (MRP) and γ-glutamylcysteine synthetase (γ-GCS) heavy subunit genes are coordinately overexpressed in cisplatin-resistant human leukemia cells (T. Ishikawa et al. J. Biol. Chem., 271: 14981-14988, 1996). Using the RNase protection assay, we examined expression levels of these genes in colon tumor and nontumorous biopsy specimens from 32 cancer patients who had not been treated with chemotherapy. Increased mRNA levels (P < 0.001) of MRP and γ-GCS genes were observed in 16 (50%) and 20 (62%) tumor samples, respectively. More importantly, all of the 16 (100%) MRP-overexpressing tumor specimens also exhibited higher levels of γ-GCS mRNA than those in the matched nontumorous specimens. The correlation coefficient between MRP and γ-GCS mRNA levels was r = 0.78 for all of the tumor samples studied. These results strongly suggest that MRP and γ-GCS genes are coordinately up-regulated during colorectal carcinogenesis.