Carcinogenesis Advance Access originally published online on October 7, 2004
Carcinogenesis 2005 26(1):209-217; doi:10.1093/carcin/bgh302
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Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.
ARTICLE |
Targeted over-expression of mPGES-1 and elevated PGE2 production is not sufficient for lung tumorigenesis in mice
1 Department of Medicine and 2 Department of Pharmacology, University of Colorado Health Science Center, Denver, CO 80262, USA, 3 Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206, USA and 4 Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA
5 To whom correspondence should be addressed Email: raphael.nemenoff{at}uchsc.edu
There is a significant body of evidence suggesting that enzymes involved in arachidonic acid metabolism and their eicosanoid products play a role in various cancers, having both pro- and antitumorigenic effects. The goal of this study was to further define the role microsomal prostaglandin E synthases (mPGES-1) play in lung tumorigenesis. Transgenic mice were created with targeted over-expression of human mPGES-1 in the alveolar and airway epithelial cells using an SP-C promoter driven construct. Transgene positive (mPGES-1+) mice were shown to significantly over-express functional mPGES-1 in the lung and more specifically in alveolar type II cells. To study the effects of mPGES-1 over-expression in lung tumor formation, mice were exposed to a complete carcinogen protocol with a single injection of urethane or an initiation/promotion model with a single injection of 3-methylcholanthrene (MCA) followed by multiple injections of butylated hydroxytoluene (BHT). mPGES-1+ mice did not show a significant difference in tumor multiplicity or tumor size at 10, 16, 19 or 30 weeks after urethane injection compared with mPGES-1– mice. No significant difference was seen in tumor incidence, multiplicity or size at 19 weeks after treatment with MCA/BHT. Western blots verified that mPGES-1 expression was increased in tumors versus uninvolved tissue of both mPGES-1+ and mPGES-1– mice with overall expression being significantly higher in mPGES-1+ mice. Cyclooxygenase-2 levels were elevated in tumors in both groups. From these studies we conclude that over-expression of mPGES-1 and highly elevated PGE2 production are not sufficient to induce lung tumors.
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