Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: We detect the expression of CES1A1, CES2, and CES3 carboxylesterase genes in human colon tumors. We were unable to detect the hBr-3 (also called hCE-3) in human liver, colon, or brain. We find large interindividual variation, >/=150-fold, for both CES1A1 and CES3 genes, 23-fold for CES2, and 66-fold for topoisomerase I. Only CES2 gene expression correlated with the carboxylesterase activity assays (P < 0.01) with CPT-11 and 4-methylumbelliferyl acetate as substrates. Nondenaturing activity gel electrophoresis showed that CES2 was the most predominant activity. Topoisomerase I gene expression significantly correlated with topoisomerase I activity (P < 0.01) in the colon tumors, but interindividual variation was very high. CONCLUSIONS: We conclude that CES2 is the most abundant carboxylesterase in colon tumors that is responsible for CPT-11 hydrolysis. This pilot study reinforces the hypothesis that there is a large interindividual variation in expression of carboxylesterases that may contribute to variation in therapeutic outcome and/or toxicity of CPT-11 therapy for colon cancer.
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Authors | Sonal P Sanghani, Sara K Quinney, Tyler B Fredenburg, Zejin Sun, Wilhelmina I Davis, Daryl J Murry, Oscar W Cummings, David E Seitz, William F Bosron |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 9
Issue 13
Pg. 4983-91
(Oct 15 2003)
ISSN: 1078-0432 [Print] United States |
PMID | 14581373
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Umbelliferones
- 4-methylumbelliferyl acetate
- RNA
- Irinotecan
- Hydrolases
- Carboxylic Ester Hydrolases
- Carboxylesterase
- DNA Topoisomerases, Type I
- Camptothecin
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Topics |
- Blotting, Northern
- Blotting, Western
- Brain
(metabolism)
- Camptothecin
(analogs & derivatives, metabolism)
- Carboxylesterase
(metabolism)
- Carboxylic Ester Hydrolases
(biosynthesis, metabolism)
- Cell Line, Tumor
- Colon
(metabolism)
- Colonic Neoplasms
(enzymology, metabolism)
- DNA Topoisomerases, Type I
(metabolism)
- Electrophoresis, Polyacrylamide Gel
- Female
- Humans
- Hydrolases
(metabolism)
- Hydrolysis
- Irinotecan
- Liver
(metabolism)
- Male
- RNA
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Umbelliferones
(metabolism)
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