Correlation between type II nitric oxide synthase and p53 expression in oral squamous cell carcinoma

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      Prolonged nitric oxide (NO) production by the enzyme type II nitric oxide synthase (NOS2) has been implicated in angiogenesis and metastasis of human cancers. In animal models, wild-type p53 (but not mutant) protein results in down-regulation of NOS2 ex pression, which reduces both tumour growth and dissemination. In the current study, we aimed to find out whether a correlation was present in oral squamous cell carcinoma. Fifty-six cases of squamous cell carcinoma were assessed immunohistochemically usi ng antibodies to NOS2 and p53 (clone DO-7). We also confirmed NOS2 protein expression in selected cases using immunoblotting. The results were correlated with clinicopathological findings. Statistical analysis showed a significant relationship between p5 3 and NOS2 expression (P= 0.001). No relationship was found between size of tumour or histological degree of differentiation, and NOS2 expression in the primary tumour.
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        • Bernnan PA
        • Downie IP
        • Landgon JD
        • Zaki GA
        Emerging role of nitric oxide in cancer.
        Br J Oral Maxillofac Surg. 1999; 37: 370-373
        • Forstermann U
        • Kleinert H
        Nitric oxide synthase: expression and expressional control of the three isoforms.
        Naunyn-Schmiedebergs Arch Pharmacol. 1995; 352: 351-364
        • Kröncke KD
        • Fehsel K
        • Kolb-Bachofen V
        Inducible nitric oxide synthase and its product nitric oxide, a small molecule with complex biological activities.
        Biol Chem HoppeSeyler. 1995; 376: 327-343
        • Radomski MW
        • Jenkins DC
        • Holmes L
        • Moncada S
        Human colorectal adenocarcinoma cells: differential nitric oxide synthesis determines their ability to aggregate platelets.
        Cancer Res. 1991; 51: 6073-6078
        • Sherman PA
        • Laubach VE
        • Reep BR
        • Wood ER
        Purification and cDNA sequence of an inducible nitric oxide synthase from a tumour cell line.
        Biochemistry. 1993; 32: 11600-11605
        • Miles DW
        • Happerfield LC
        • Thomsen LL
        • Filipe I
        Nitric oxide synthase and localisation in gastric carcinoma.
        Proceedings of the American Association of Cancer Research. 1996; 37: 154
        • Thomsen LL
        • Lawton FG
        • Knowles RG
        • Beesley JE
        • Riveros-Moreno V
        • Moncada S
        Nitric oxide synthase activity in human gynecological cancer.
        Cancer Res. 1994; 54: 1352-1354
        • Sagar SM
        • Singh G
        • Hodson I
        • Whitton AC
        Nitric oxide and anti-cancer therapy.
        Cancer Treat Rev. 1995; 21: 159-181
        • Wink DA
        • Vodovotz Y
        • Laval D
        • Laval F
        • Dewhirst DW
        • Mitchell JB
        The multifaceted roles of nitric oxide in cancer.
        Carcinogenesis. 1998; 19: 711-721
        • Albina JE
        • Reichner JS
        Role of nitric oxide in mediation of macrophage cytotoxicity and adoptosis.
        Cancer Metastasis Rev. 1998; 17: 39-53
        • Thomsen LL
        • Miles DW
        Role of nitric oxide in tumour progression: lessons from human tumours.
        Cancer Metastasis Rev. 1998; 17: 107-118
        • Rosbe KW
        • Prazma J
        • Petrusz P
        • Mims W
        • Ball SS
        • Weissler MC
        Immunohistochemical characterisation of nitric oxide synthase activity in squamous cell carcinoma of the head and neck.
        Otolaryngol Head Neck Surg. 1995; 113: 541-549
        • Gavilanes J
        • Moro MA
        • Lizasoain I
        Nitric oxide synthase activity in human squamous cell carcinoma of the head and neck.
        Larygoscope. 1999; 109: 148-152
        • Gallo O
        • Masini E
        • Morbidelli L
        Role of nitric oxide in angiogenesis and tumour progression in head and neck cancer.
        J Natl Cancer Inst. 1998; 90: 587-596
        • Ambs S
        • Hussain SP
        • Harris CC
        Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression.
        FASEB J. 1997; 11: 443-448
        • Ambs S
        • Ogunfusika MO
        • Merriam WG
        • Bennet WP
        • Billiar TR
        • Harris CC
        Up-regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice.
        Proc Natl Acad Sci USA. 1998; 95: 8823-8828
        • Messmer UK
        • Ankacrona M
        • Nicotera P
        • Brune B
        p53 expression in nitric oxide-induced apoptosis.
        FEBS Lett. 1994; 355: 23-26
        • Forrester K
        • Ambs S
        • Lupold SE
        Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase (NOS2) by wild-type p53.
        Proc Natl Acad Sci USA. 1996; 93: 2442-2447
        • Ho YS
        • Wang YJ
        • Lin JK
        Induction of p53 and p21/WAF1/CIP1 expression by nitric oxide and their association with apoptosis in human cancer cells.
        Mol Carcinog. 1996; 16: 20-31
        • Vogelstein B
        Cancer: A deadly inheritance.
        Nature. 1990; 348: 681-682
        • Dameron KM
        • Volpert OV
        • Tainsky MA
        • Bouck N
        Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1.
        Science. 1994; 265: 1582-1584
        • Mukhopadhyay D
        • Tsiokas L
        • Sukhatme VP
        Wild-type p53 and v-src exert opposing influences on human vascular endothelial growth gene expression.
        Cancer Res. 1995; 55: 6161-6165
        • Ogden GR
        • Kiddie RA
        • Lunny DP
        • Lane DP
        Assessment of p53 protein expression in normal, benigin and malignant oral mucosa.
        J Pathol. 1992; 166: 389-394
        • Field JK
        • Spandidos DA
        • Malliri A
        • Gosney JR
        • Yiagnisis M
        • Stell PM
        Elevated p53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head neck.
        Br J Cancer. 1991; 64: 573-577
        • Shin DM
        • Kim J
        • Ro JY
        Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis.
        Cancer Res. 1994; 54: 321-326
        • Partridge M
        • Kiguwa S
        • Emilion G
        • Pateromichelakis S
        • A'Hearn R
        • Langdon JD
        New insights into p53 protein stabilisation in oral squamous cell carcinoma.
        Oral Oncol. 1999; 35: 45-55
        • Brennan PA
        • Umar T
        • Buckley J
        • Zaki GA
        • Spedding AV
        • Langdon JD
        Nitric oxide synthase expression in pleomorphic adenoma of the parotid.
        Br J Oral Maxillofac Surg. 2000; 38: 338-342
        • Richter N
        • Petersson AS
        • Wennmalm A
        • Schimke I
        Detection of an approximately 100 kD protein with strong immunoreactivity to antibodies specific for inducible nitric oxide synthase (iNOS) but without NOS activity in neutrophils of patients suffering from sepsis: results a preliminary study.
        Inflamm Res. 1999; 48: 651-656
        • Bentz B
        • Haynees GK
        • Lingen MW
        • Pelzer HJ
        • Hanson DG
        • Radosevich JA
        Nitric oxide synthase type 3 is increased in squamous cell hyperplasia, dysplasia, and squamous cell carcinoma of the head and neck.
        Ann Otal Rhinol Laryngol. 1999; 108: 781-787
        • Macmicking J
        • Xie QW
        • Nathan C
        Nitric oxide and macrophage function.
        Annu Rev Immunol. 1997; 15: 323-350
        • Hajri A
        • Metzger E
        • Vallat F
        Role of nitric oxide in pancreatic tumour growth: in vivo and in vitro studies.
        Br J Cancer. 1998; 78: 841-849
        • Thomas C
        • Nijenhuis AM
        • Dontje B
        • Daemen T
        • Scgerphof GL
        Tumoricidal responses of liver macrophages isolated from rats bearing liver metastases of colonic adenocarcinoma.
        J Leukoc Biol. 1995; 57: 617-623
        • Thomsen L
        • Scott JMJ
        • Topley P
        • Knowles RG
        • Keerie AJ
        • Frend AJ
        Selective inhibition of inducible nitric oxide synthase inhibits tumour growth in vivo: studies with 1400W, a novel inhibitor.
        Cancer Res. 1997; 57: 3300-3304