Overexpression of 5-lipoxygenase and its relation with cell proliferation and angiogenesis in 7,12-dimethylbenz(α)anthracene-induced rat mammary carcinogenesis.

Abstract

The present study was performed to investigate the critical role of 5-lipoxygenase (5-LOX) in 7,12-dimethylbenz(α)anthracene (DMBA)-induced rat mammary inflammation associated carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(α)anthracene (DMBA; 0.5 mg/100 g body weight) by a single tail vein injection, followed by administration of zileuton (2000 mg/kg diet) from week 7 until the termination of the study at 31 wk. 5-LOX protein expression, 5-hydroxyeicosatetraenoic acid (5-HETE), and leukotriene B4 (LTB4 ) production in rat mammary tissue were analyzed at 6, 12, and 24 wk post-DMBA injection. Rate of cell proliferation was analyzed by bromodioxyuridine labeling index (BrdU-LI). Microvessel density, level of VEGF, and MMP-2 were also measured. DMBA induces inflammation in rat mammary gland as early as 6 wk. 5-LOX is upregulated in DMBA treated rats right from 6 wk when compared with their normal counterparts. An overexpression of 5-LOX is accompanied with increase in 5-HETE, LTB4 production and high BrdU-LI with an increase of two key angiogenic factors for tumorigenesis; MMP-2 and VEGF. It was found that 5-LOX specific inhibitor brought about substantial protection against DMBA-induced mammary carcinogenesis. Histological findings showed substantial repair of hyperplastic lesions. There was a significant reduction in the rate of cell proliferation and expression of angiogenic factors, MMP-2 and VEGF. 5-LOX plays an important role in DMBA-induced inflammation associated carcinogenesis via activation of MMP-2 and VEGF. 5-LOX expression can be considered as a critical event in controlling the process of mammary tumor development.

• Authors: Mary Chatterjee, Subhadeep Das, Kaushik Roy, Malay Chatterjee
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 52 Issue 5 Pg. 359-69 (May 2013) ISSN: 1098-2744 [Electronic] United States
• PMID: 22213124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Hydroxyeicosatetraenoic Acids
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Leukotriene B4
• 5-hydroxy-6,8,11,14-eicosatetraenoic acid
• 9,10-Dimethyl-1,2-benzanthracene
• Arachidonate 5-Lipoxygenase
• Matrix Metalloproteinase 2

Topics

• 9,10-Dimethyl-1,2-benzanthracene (toxicity)
• Animals
• Arachidonate 5-Lipoxygenase (metabolism)
• Cell Proliferation
• Female
• Hydroxyeicosatetraenoic Acids (metabolism)
• Leukotriene B4 (metabolism)
• Mammary Neoplasms, Experimental (blood supply, chemically induced, metabolism, pathology)
• Matrix Metalloproteinase 2 (metabolism)
• Microvessels (metabolism)
• Rats
• Rats, Sprague-Dawley
• Vascular Endothelial Growth Factor A (metabolism)