title: Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth.
abstract: Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the β-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS(-/-)  mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth.
authors: Animal Facility, National Institute of Tumours G. Pascale, Naples, Italy.
authors: Antonio
authors: A
authors: Barbieri
authors: Giuseppe
authors: G
authors: Palma
authors: Alessandra
authors: A
authors: Rosati
authors: Aldo
authors: A
authors: Giudice
authors: Antonia
authors: A
authors: Falco
authors: Antonella
authors: A
authors: Petrillo
authors: Mario
authors: M
authors: Petrillo
authors: Sabrina
authors: S
authors: Bimonte
authors: Maria
authors: M
authors: Di Benedetto
authors: Giuseppe
authors: G
authors: Esposito
authors: Paola
authors: P
authors: Stiuso
authors: Alberto
authors: A
authors: Abbruzzese
authors: Michele
authors: M
authors: Caraglia
authors: Claudio
authors: C
authors: Arra
mesh_terms: D000818:Animals; D002908:Chronic Disease; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D011943:Receptors, Adrenergic, beta; D052250:Nitric Oxide Synthase Type III