AIM: Previously, we identified a natural mutant of hepatitis B virus X gene (HBx) with a deletion from 382 to 401 base pairs (termed HBxDelta127), which could potently enhance growth of hepatoma cells. In this study, we further investigated the mechanism of increased hepatoma cell growth that was mediated by HBxDelta127. METHODS: We examined the effect of HBxDelta127 on the transcription factor sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS) in a model of HepG2-XDelta127 (or H7402-XDelta127) cells, which was stably transfected with HBxDelta127 gene in a human hepatoma HepG2 (or H7402) cell line. RESULTS: Relative to wild type HBx, HBxDelta127 was able to potently activate SREBP-1c at the levels of promoter activity, mRNA and protein by a luciferase reporter gene assay, RT-PCR and Western blot analysis. Then, using the treatment with MK886, a specific 5-lipoxygenases (5-LOX) inhibitor, (or 5-LOX siRNA) we identified that 5-LOX was responsible for the upregulation of SREBP-1c by luciferase reporter gene assay, RT-PCR and Western blot analysis. Because FAS was a target gene of SREBP-1c, we further showed that HBxDelta127 was able to strongly activate the promoter activity of FAS and upregulated the mRNA expression level of FAS as well, by luciferase reporter gene assay and RT-PCR. In function, flow cytometry analysis revealed that FAS contributed to the growth of hepatoma cells that was mediated by HBxDelta127, using cerulenin (a FAS inhibitor). CONCLUSION: HBxDelta127 promotes hepatoma cell growth through activating SREBP-1c involving 5-LOX.
AIM: Previously, we identified a natural mutant of hepatitis B virus X gene (HBx) with a deletion from 382 to 401 base pairs (termed HBxDelta127), which could potently enhance growth of hepatoma cells. In this study, we further investigated the mechanism of increased hepatoma cell growth that was mediated by HBxDelta127. METHODS: We examined the effect of HBxDelta127 on the transcription factor sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS) in a model of HepG2-XDelta127 (or H7402-XDelta127) cells, which was stably transfected with HBxDelta127 gene in a humanhepatoma HepG2 (or H7402) cell line. RESULTS: Relative to wild type HBx, HBxDelta127 was able to potently activate SREBP-1c at the levels of promoter activity, mRNA and protein by a luciferase reporter gene assay, RT-PCR and Western blot analysis. Then, using the treatment with MK886, a specific 5-lipoxygenases (5-LOX) inhibitor, (or 5-LOX siRNA) we identified that 5-LOX was responsible for the upregulation of SREBP-1c by luciferase reporter gene assay, RT-PCR and Western blot analysis. Because FAS was a target gene of SREBP-1c, we further showed that HBxDelta127 was able to strongly activate the promoter activity of FAS and upregulated the mRNA expression level of FAS as well, by luciferase reporter gene assay and RT-PCR. In function, flow cytometry analysis revealed that FAS contributed to the growth of hepatoma cells that was mediated by HBxDelta127, using cerulenin (a FAS inhibitor). CONCLUSION: HBxDelta127 promotes hepatoma cell growth through activating SREBP-1c involving 5-LOX.
Authors: H Tu; C Bonura; C Giannini; H Mouly; P Soussan; M Kew; P Paterlini-Bréchot; C Bréchot; D Kremsdorf Journal: Cancer Res Date: 2001-11-01 Impact factor: 12.701
Authors: Johannes V Swinnen; Paul P Van Veldhoven; Leen Timmermans; Ellen De Schrijver; Koen Brusselmans; Frank Vanderhoydonc; Tine Van de Sande; Hannelore Heemers; Walter Heyns; Guido Verhoeven Journal: Biochem Biophys Res Commun Date: 2003-03-21 Impact factor: 3.575
Authors: Carolina González; David Tabernero; Maria Francesca Cortese; Josep Gregori; Rosario Casillas; Mar Riveiro-Barciela; Cristina Godoy; Sara Sopena; Ariadna Rando; Marçal Yll; Rosa Lopez-Martinez; Josep Quer; Rafael Esteban; Maria Buti; Francisco Rodríguez-Frías Journal: World J Gastroenterol Date: 2018-05-21 Impact factor: 5.742