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Effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2010 Sep; Vol. 27 (3), pp. 960-7. Date of Electronic Publication: 2009 Sep 23. - Publication Year :
- 2010
-
Abstract
- The effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells were unclear by now. In this study, we detected the gene expression of multiple drug resistance-associated proteins (MRP) in RMG-I-H cells and RMG-I-H cells treated with anti-Lewis Y monoclonal antibody to investigate the association between Lewis Y antigen and the gene expression of drug resistance-associated proteins. Compared with RMG-I cells, the expression of MRP1, MRP2, protein kinase C-alpha (PKC-alpha), and topoisomerase I (Topo I) mRNAs in RMG-I-H cells were significantly upregulated, while the MDR-1 mRNA was downregulated. Immunochemistry analyses indicated that the in vitro and in vivo expression levels of MDR-1 protein (P-gp) in RMG-I-H cells were significantly higher than those in RMG-I cells. After RMG-I-H cells were treated with anti-Lewis Y monoclonal antibody, the expression levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs gradually decreased with the prolongation of treatment duration. In contrast, no obvious changes were noted in the expression levels of these mRNAs in the non-treatment group. At 6 h after treatment, the relative levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs in the antibody treatment group were significantly lower than those in the non-treatment group. In conclusion, Lewis Y antigen is closely associated with regulating the gene expression of multiple drug resistance-associated proteins.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Adenocarcinoma, Clear Cell genetics
Adenocarcinoma, Clear Cell metabolism
Animals
Antibodies, Monoclonal pharmacology
Cell Line, Tumor drug effects
Cell Line, Tumor metabolism
DNA Topoisomerases, Type I biosynthesis
DNA Topoisomerases, Type I genetics
Female
Fucosyltransferases physiology
Humans
Lewis Blood Group Antigens immunology
Mice
Mice, Nude
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins biosynthesis
Multidrug Resistance-Associated Proteins genetics
Neoplasm Proteins genetics
Neoplasm Transplantation
Ovarian Neoplasms genetics
Ovarian Neoplasms metabolism
Protein Kinase C-alpha biosynthesis
Protein Kinase C-alpha genetics
RNA, Messenger biosynthesis
RNA, Messenger genetics
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
Recombinant Fusion Proteins physiology
Transfection
Galactoside 2-alpha-L-fucosyltransferase
Adenocarcinoma, Clear Cell pathology
Drug Resistance, Multiple genetics
Drug Resistance, Neoplasm genetics
Gene Expression Regulation, Neoplastic
Lewis Blood Group Antigens physiology
Neoplasm Proteins biosynthesis
Ovarian Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 27
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 19771531
- Full Text :
- https://doi.org/10.1007/s12032-009-9317-6