Anticancer Research · Nov 2018

BUBR1 Insufficiency Is Correlated with eNOS Reduction Experimentally In Vitro and In Vivo, and in Gastric Cancer Tissue

By Kawakubo E, Matsumoto T, Yoshiya K et al.

BACKGROUND/AIM: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and human gastric cancer tissues. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNA-transfected HUVECs. Additionally, guanosine 3',5' cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficient mice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in human gastric cancer tissues. RESULTS: BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNA-transfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. CONCLUSION: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation.

doi.org/10.21873/anticanres.12960 Open access PubMed 30396924 Mechanisms