Reduced expression of 15-lipoxygenase 2 in human head and neck carcinomas. Tumour Biol 2006;27(5):261-73
Date
07/29/2006Pubmed ID
16874012DOI
10.1159/000094761Scopus ID
2-s2.0-33747508165 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have demonstrated cancer chemoprevention effects associated with their ability to modulate polyunsaturated fatty acid metabolism. In the present study, we report a significant reduction of 15-lipoxygenase 2 (15-LOX-2) in seven carcinoma cell lines of the human head and neck when compared with normal primary cultured keratinocytes, and 18 primary head and neck squamous cell carcinomas (HNSCC) when compared with matched normal mucosa. 15-LOX-2 is mainly expressed in the mature cells of the benign squamous epithelium, but not in the basal layer cells of benign epithelium, suggesting a role of 15-LOX-2 in cell differentiation. We further found that 15-lipoxygenase activity was reduced in carcinoma cells when compared with normal primary cultured keratinocytes. When the effects of NSAIDs were examined on cell proliferation and regulation of 15-LOX-2 in the carcinoma cells, NS398 treatment resulted in significant growth inhibition associated with upregulation of 15-LOX-2 and its major metabolite 15-S-HETE. Finally, restoration of 15-LOX-2 expression into these carcinoma cells significantly inhibited cell proliferation. Our results demonstrate that 15-LOX-2 expression is significantly reduced and this reduction may promote proliferation in human head and neck carcinoma. 15-LOX-2 may be a possible biomarker in human head and neck malignancy.
Author List
Wang D, Chen S, Feng Y, Yang Q, Campbell BH, Tang X, Campbell WBAuthors
Bruce H. Campbell MD Emeritus Professor in the Otolaryngology department at Medical College of WisconsinWilliam B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Arachidonate 15-LipoxygenaseCarcinoma
Carcinoma, Squamous Cell
Cell Proliferation
Cells, Cultured
Gene Expression Regulation, Enzymologic
Head and Neck Neoplasms
Humans
Keratinocytes
Nitrobenzenes
Sulfonamides
Tumor Cells, Cultured