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

Abstract

We have recently shown that multidrug resistance-associated protein (MRP) and gamma-glutamylcysteine synthetase (gamma-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 gamma-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 gamma-GCS mRNA than those in the matched nontumorous specimens. The correlation coefficient between MRP and gamma-GCS mRNA levels was r = 0.78 for all of the tumor samples studied. These results strongly suggest that MRP and gamma-GCS genes are coordinately up-regulated during colorectal carcinogenesis.

• Authors: M T Kuo, J J Bao, S A Curley, M Ikeguchi, D A Johnston, T Ishikawa
• Journal: Cancer research (Cancer Res) Vol. 56 Issue 16 Pg. 3642-4 (Aug 15 1996) ISSN: 0008-5472 [Print] United States
• PMID: 8705999 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP-Binding Cassette Transporters
• Multidrug Resistance-Associated Proteins
• RNA, Messenger
• Glutamate-Cysteine Ligase

Topics

• ATP-Binding Cassette Transporters (genetics)
• Base Sequence
• Colorectal Neoplasms (metabolism)
• Gene Expression Regulation, Neoplastic
• Glutamate-Cysteine Ligase (genetics)
• Humans
• Molecular Sequence Data
• Multidrug Resistance-Associated Proteins
• RNA, Messenger (analysis)