Reduced expression of 15-lipoxygenase 2 in human head and neck carcinomas.
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.
Wang
Dian
D
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisc., USA. dwang@radonc.mcw.edu
Chen
Shaoying
S
Feng
Ying
Y
Yang
Qiuhui
Q
Campbell
Bruce H
BH
Tang
Xin
X
Campbell
William B
WB
D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002277:Carcinoma / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell; D049109:Cell Proliferation; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D009578:Nitrobenzenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase