Antioxidative response for nitric oxide production in breast carcinoma.
Our aim was to study the role of oxidant and nitric oxide (NO)-derived damage in human breast carcinomas by studying the expression of nitrotyrosine in tumor tissue. To elucidate whether nitrotyrosine levels associate with NO synthesis and have an effect on antioxidative enzyme response or angiogenesis, we also studied the expression of all three nitric oxide synthases (NOS), manganese superoxide dismutase (MnSOD), catalase and vascular endothelial growth factor (VEGF) in the tumors. A large set of breast cancer samples in microarray blocks were stained with antibodies to nitrotyrosine, iNOS, eNOS, nNOS, MnSOD, catalase and VEGF. Nitrotyrosine expression was seen in 56% of the cases. There was a close relationship between the expression of nitrotyrosine and all three NOS isoforms (for all p<0.0005), catalase (p<0.0005) and MnSOD (p=0.043), in addition enlarged tumor size was in association with high nitrotyrosine (p=0.046), eNOS (p=0.005) and VEGF (p=0.046) levels. Our findings suggest that NO-derived oxidative damage takes place and its level associates to NOS synthesis in human breast cancer. The current results also imply the attempt of cells to hedge against effects of NO by increasing their MnSOD and catalase expression.
Karihtala
Peeter
P
Department of Pathology, University of Oulu and Oulu University Hospital, FIN-90014 Oulu, Finland.
Kinnula
Vuokko L
VL
Soini
Ylermi
Y
D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary; D002374:Catalase / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020033:Protein Isoforms; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase