MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, Y. Y.
Right arrow Articles by Lazo, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Y. Y.
Right arrow Articles by Lazo, J. S.

Human metallothionein isoform gene expression in cisplatin-sensitive and resistant cells

YY Yang, ES Woo, CE Reese, RR Bahnson, N Saijo and JS Lazo

Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.

Overexpression of metallothioneins (MTs) has been observed in some cis- diamminedichloroplatinum (CDDP)-resistant cells. We have developed oligonucleotide probes for each of the six non-neuronal human MT (hMT) isoforms and used them to assay hMT isoform expression in three pairs of CDDP-resistant and -sensitive human carcinoma cell lines, i.e., SCC25/CP versus SCC25 cells, H69/CP versus H69 cells, and SW2/CP versus SW2 cells. We found a 9-fold increase in basal hMT-IIa mRNA levels and a 5-fold increase in hMT-le mRNA levels in SCC25/CP cells, compared with SCC25 cells. Nuclear run-on studies also revealed a 3-fold increase in hMT-IIa transcription rate. Basal hMT-IIa steady state mRNA levels were 2-3.6-fold greater in H69/CP and SW2/CP cells, compared with their parental cells. No significant basal expression of hMT-Ia, - Ib, -If, or Ig was detected in any cells, suggesting that overexpression of these isoforms was not commonly associated with the CDDP-resistant phenotype. Levels of constitutively expressed hMT isoforms, as well as hMT-If, could be elevated by treatment of all cells with 100 microM zinc. The universal overexpression of hMT-IIa suggests a role of this particular isoform in CDDP resistance. Using our isoform-specific hMT-IIa probe and the demethylating agent 5'- azacytidine (AZC), we found that AZC pretreatment increased basal hMT- IIa mRNA levels in SCC25 but not SCC25/CP cells, suggesting that DNA hypomethylation was responsible for higher basal hMT-IIa mRNA levels in SCC25/CP cells. AZC had little or no effect on hMT-If or -Ig expression. Limited restriction analysis by methylation-sensitive enzymes, however, revealed no obvious differences in the methylation status of the hMT-IIa promoter in either SCC25 or SCC25/CP cells.

Volume 45, Issue 3, pp. 453-460, 03/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
D.-W. Shen, X.-J. Liang, T. Suzuki, and M. M. Gottesman
Identification by Functional Cloning from a Retroviral cDNA Library of cDNAs for Ribosomal Protein L36 and the 10-kDa Heat Shock Protein that Confer Cisplatin Resistance
Mol. Pharmacol., April 1, 2006; 69(4): 1383 - 1388.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics