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Br J Cancer. 1995 July; 72(1): 41–44.
PMCID: PMC2034139

Nitric oxide synthase activity in human breast cancer.

Abstract

Nitric oxide (NO) is generated by a family of isoenzymes (NO synthases) expressed in a wide range of mammalian cells. We have recently reported NO synthase expression in human gynaecological cancers. In this study we have assessed the activity and distribution of NO synthase in a series of human breast tumours and in normal breast tissue. Calcium-dependent (constitutive) and -independent (inducible) NO synthase activity, as well as NO biosynthesis, was high in invasive tumours compared with benign or normal tissue. Furthermore, for invasive ductal carcinomas, NO biosynthesis was significantly greater for grade III compared with grade II tumours. Immunohistochemical investigations revealed immunolabelling with a monoclonal antibody to murine inducible NO synthase predominantly within tumour-associated macrophages. Immunolabelling with a polyclonal antiserum raised against rat brain NO synthase was also observed in vascular endothelial and myoepithelial cells. Thus NO synthase is expressed in human breast tumours, where its presence correlates with tumour grade.

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Selected References

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  • Andrade SP, Hart IR, Piper PJ. Inhibitors of nitric oxide synthase selectively reduce flow in tumor-associated neovasculature. Br J Pharmacol. 1992 Dec;107(4):1092–1095. [PMC free article] [PubMed]
  • Brave SR, Tucker JF, Gibson A, Bishop AE, Riveros-Moreno V, Moncada S, Polak JM. Localisation of nitric oxide synthase within non-adrenergic, non-cholinergic nerves in the mouse anococcygeus. Neurosci Lett. 1993 Oct 14;161(1):93–96. [PubMed]
  • Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. [PubMed]
  • Förstermann U, Gorsky LD, Pollock JS, Ishii K, Schmidt HH, Heller M, Murad F. Hormone-induced biosynthesis of endothelium-derived relaxing factor/nitric oxide-like material in N1E-115 neuroblastoma cells requires calcium and calmodulin. Mol Pharmacol. 1990 Jul;38(1):7–13. [PubMed]
  • Jenkins DC, Charles IG, Baylis SA, Lelchuk R, Radomski MW, Moncada S. Human colon cancer cell lines show a diverse pattern of nitric oxide synthase gene expression and nitric oxide generation. Br J Cancer. 1994 Nov;70(5):847–849. [PMC free article] [PubMed]
  • Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J. 1994 Mar 1;298(Pt 2):249–258. [PubMed]
  • Li LM, Kilbourn RG, Adams J, Fidler IJ. Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. Cancer Res. 1991 May 15;51(10):2531–2535. [PubMed]
  • Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. [PubMed]
  • Miles DW, Happerfield LC, Naylor MS, Bobrow LG, Rubens RD, Balkwill FR. Expression of tumour necrosis factor (TNF alpha) and its receptors in benign and malignant breast tissue. Int J Cancer. 1994 Mar 15;56(6):777–782. [PubMed]
  • Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed]
  • Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. [PubMed]
  • Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett. 1991 Oct 7;291(1):145–149. [PubMed]
  • Sherman PA, Laubach VE, Reep BR, Wood ER. Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry. 1993 Nov 2;32(43):11600–11605. [PubMed]
  • Springall DR, Riveros-Moreno V, Buttery L, Suburo A, Bishop AE, Merrett M, Moncada S, Polak JM. Immunological detection of nitric oxide synthase(s) in human tissues using heterologous antibodies suggesting different isoforms. Histochemistry. 1992 Nov;98(4):259–266. [PubMed]
  • Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino MA, Jr, Shepard HM. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985 Nov 22;230(4728):943–945. [PubMed]
  • Terenghi G, Riveros-Moreno V, Hudson LD, Ibrahim NB, Polak JM. Immunohistochemistry of nitric oxide synthase demonstrates immunoreactive neurons in spinal cord and dorsal root ganglia of man and rat. J Neurol Sci. 1993 Aug;118(1):34–37. [PubMed]
  • Thomsen LL, Ching LM, Zhuang L, Gavin JB, Baguley BC. Tumor-dependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice. Cancer Res. 1991 Jan 1;51(1):77–81. [PubMed]
  • Thomsen LL, Lawton FG, Knowles RG, Beesley JE, Riveros-Moreno V, Moncada S. Nitric oxide synthase activity in human gynecological cancer. Cancer Res. 1994 Mar 1;54(5):1352–1354. [PubMed]
  • Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. [PubMed]
  • Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Mayer B, Reibnegger G, Weiss G, Wachter H. Ca2+/calmodulin-dependent nitric oxide synthase activity in the human cervix carcinoma cell line ME-180. Biochem J. 1993 Jan 15;289(Pt 2):357–361. [PubMed]
  • Wood PJ, Stratford IJ, Adams GE, Szabo C, Thiemermann C, Vane JR. Modification of energy metabolism and radiation response of a murine tumour by changes in nitric oxide availability. Biochem Biophys Res Commun. 1993 Apr 30;192(2):505–510. [PubMed]

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