title: The expression of iNOS and nitrotyrosine in colitis and colon cancer in humans.
abstract: Chronic inflammation increases the risk of development of several types of malignancies including colon cancer. It also represents a paradigm for the connection between inflammation and cancer in terms of epidemiology and mechanistic studies in preclinical models. A key component of inflammation promoting cancer is the transcription factor NF-κB, which is known to play a critical role in the regulation of the inducible nitric oxide synthase (iNOS) gene. iNOS is an enzyme dominantly expressed during inflammatory reactions. Although synthesis of high amounts of nitric oxide (NO) by iNOS has been demonstrated in pathophysiological processes, such as acute or chronic inflammation and tumorigenesis, the role of iNOS activity in these diseases is still not well understood. Analysis of human biopsies of colitis and colon cancer using immunohistochemistry revealed elevated iNOS protein expression levels, which were strongly paralleled by increased expression of nitrotyrosine suggesting that iNOS has been highly activated in these tissues. These results were corroborated in an in vitro study showing the presence of high iNOS levels in a colon cancer cell line (HT-29) following inflammatory stimuli (TNF-α, peroxynitrite). In addition, the involvement of metastatic processes in the colon biopsies was assessed by means of in situ zymography of MMP activation. MMP 2 (gelatinase A) activation was higher in histopathological sections of colitis and cancer compared to controls. Overall, these data strengthen the findings that in inflammation and colon cancer in humans, iNOS expression and tyrosine nitration may be an indicator of cancer development and progression.
authors.affiliation: Department of Anatomy and Cell Biology, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Gochman
authors.forename: Jamal
authors.initials: J
authors.lastname: Mahajna
authors.forename: Pessia
authors.initials: P
authors.lastname: Shenzer
authors.forename: Aviva
authors.initials: A
authors.lastname: Dahan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Blatt
authors.forename: Rami
authors.initials: R
authors.lastname: Elyakim
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Reznick
mesh_terms: D003092:Colitis / Q000235:genetics* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D016328:NF-kappa B; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II