Skip Navigation

JNCI Journal of the National Cancer Institute 2003 95(14):1053-1061; doi:10.1093/jnci/95.14.1053
© 2003 by Oxford University Press
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (23)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Chen, X.
Right arrow Articles by Yang, C. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, X.
Right arrow Articles by Yang, C. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of the National Cancer Institute, Vol. 95, No. 14, 1053-1061, July 16, 2003
© 2003 Oxford University Press

ARTICLE

Leukotriene A4 Hydrolase in Rat and Human Esophageal Adenocarcinomas and Inhibitory Effects of Bestatin

Xiaoxin Chen, Ning Li, Su Wang, Nan Wu, Jungil Hong, Xiaolong Jiao, Mark J. Krasna, David G. Beer, Chung S. Yang

Affiliation of Authors: X. Chen, N. Li, S. Wang, N. Wu, J. Hong, C. S. Yang, Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway; X. Jiao, M. J. Krasna, Division of Thoracic Surgery, University of Maryland Medical System, Baltimore; D. G. Beer, Section of General Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor.

Correspondence to: Chung S. Yang, Ph.D., Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, 164 Frelinghuysen Rd., Piscataway, NJ 08854 (e-mail: csyang{at}rci.rutgers.edu).

Background: Esophageal adenocarcinoma (EAC) is increasing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator. We used this model and human EAC and non-tumor tissues to elucidate the expression pattern of LTA4H and to evaluate it as a target for chemoprevention. Methods: LTA4H expression was examined by western blotting and immunohistochemistry. The functional role of LTA4H in carcinogenesis was investigated by use of an LTA4H inhibitor, bestatin, in the rat EGDA model. All statistical tests were two-sided. Results: LTA4H was overexpressed in all 10 rat EACs examined, compared with its level in normal rat tissue; it was also overexpressed in four of six human EAC tumor samples, compared with its level in adjacent non-tumor tissue. In tissue sections from 20 EGDA rats and 92 patients (86 with EAC, one with dysplasia, and five with columnar-lined esophagus), LTA4H was expressed in infiltrating inflammatory cells and overexpressed in the columnar cells of preinvasive lesions and cancers, especially in well-differentiated EACs, as compared with the basal cells of the normal esophageal squamous epithelium. Bestatin statistically significantly inhibited LTB4 biosynthesis in the esophageal tissues of EGDA rats (without bestatin = 8.28 ng/mg of protein; with bestatin = 4.68 ng/mg of protein; difference = 3.60, 95% CI = 1.59 to 5.61; P = .002) and reduced the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats) (difference = 31.6%, 95% CI = 0.3% to 56.2%; P = .042). Conclusion: LTA4H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of EAC.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 NEJMHome page
M. Peters-Golden and W. R. Henderson Jr.
Leukotrienes
N. Engl. J. Med., November 1, 2007; 357(18): 1841 - 1854.
[Full Text] [PDF]

Home page
 CarcinogenesisHome page
Z. Sun, S. Sood, N. Li, D. Ramji, P. Yang, R. A. Newman, C. S. Yang, and X. Chen
Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors
Carcinogenesis, September 1, 2006; 27(9): 1902 - 1908.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Arguello, S. Paz, E. Hernandez, C. Corriveau-Bourque, L. M. Fawaz, J. Hiscott, and R. Lin
Leukotriene A4 Hydrolase Expression in PEL Cells Is Regulated at the Transcriptional Level and Leads to Increased Leukotriene B4 Production.
J. Immunol., June 1, 2006; 176(11): 7051 - 7061.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. G. Brock, Y.-J. Lee, E. Maydanski, T. L. Marburger, M. Luo, R. Paine III, and M. Peters-Golden
Nuclear localization of leukotriene A4 hydrolase in type II alveolar epithelial cells in normal and fibrotic lung
Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L224 - L232.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
A. H. Pande, S. Qin, and S. A. Tatulian
Membrane Fluidity Is a Key Modulator of Membrane Binding, Insertion, and Activity of 5-Lipoxygenase
Biophys. J., June 1, 2005; 88(6): 4084 - 4094.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Diaz-Perales, V. Quesada, L. M. Sanchez, A. P. Ugalde, M. F. Suarez, A. Fueyo, and C. Lopez-Otin
Identification of Human Aminopeptidase O, a Novel Metalloprotease with Structural Similarity to Aminopeptidase B and Leukotriene A4 Hydrolase
J. Biol. Chem., April 8, 2005; 280(14): 14310 - 14317.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Hoque, S. M. Lippman, T.-T. Wu, Y. Xu, Z. D. Liang, S. Swisher, H. Zhang, L. Cao, J. A. Ajani, and X.-c. Xu
Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention
Carcinogenesis, April 1, 2005; 26(4): 785 - 791.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Z. Haeggstrom
Leukotriene A4 Hydrolase/Aminopeptidase, the Gatekeeper of Chemotactic Leukotriene B4 Biosynthesis
J. Biol. Chem., December 3, 2004; 279(49): 50639 - 50642.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. T. Mao, I-H. Tsu, S. M. Dubinett, B. Adams, T. Sarafian, F. Baratelli, M. D. Roth, and K. J. Serio
Modulation of Pulmonary Leukotriene B4 Production by Cyclooxygenase-2 Inhibitors and Lipopolysaccharide
Clin. Cancer Res., October 15, 2004; 10(20): 6872 - 6878.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Chen, S. Wang, N. Wu, S. Sood, P. Wang, Z. Jin, D. G. Beer, T. J. Giordano, Y. Lin, W.-c. J. Shih, et al.
Overexpression of 5-Lipoxygenase in Rat and Human Esophageal Adenocarcinoma and Inhibitory Effects of Zileuton and Celecoxib on Carcinogenesis
Clin. Cancer Res., October 1, 2004; 10(19): 6703 - 6709.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Kaiser, H. Kamal, A. Rank, H.-J. Kolb, E. Holler, A. Ganser, B. Hertenstein, H. Mischak, and E. M. Weissinger
Proteomics applied to the clinical follow-up of patients after allogeneic hematopoietic stem cell transplantation
Blood, July 15, 2004; 104(2): 340 - 349.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
R. N. DuBois
Leukotriene A4 Signaling, Inflammation, and Cancer
J Natl Cancer Inst, July 16, 2003; 95(14): 1028 - 1029.
[Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.