BACKGROUND: The role of Epstein-Barr virus (EBV) infection in gastric carcinogenesis remains largely unknown. The authors studied the effects of zinc finger E-box binding factor 1 (ZEB1) on latent-lytic switch of EBV infection in gastric cancer and explored the importance of EBV in gastric carcinogenesis. METHODS: Loss or gain of ZEB1 function was obtained by ZEB1 small-interfering RNA (siRNA) knock-down or forced ZEB1 re-expression. Cell growth was evaluated by cell viability and colony formation assays, and the cell cycle was assessed by flow cytometry. EBV was detected using quantitative polymerase chain reaction (PCR) and in situ hybridization analyses. RESULTS: ZEB1 knock-down in a latent EBV-infected gastric cancer cell line (YCC10) increased lytic gene BamHI W leftward reading frame 1 (BZLF1) expression and decreased the expression of latent gene EB nuclear antigen 1 (EBNA1) concomitant with the inhibition of cell viability (P < .05) and S-phase DNA synthesis (P < .01). ZEB1 depletion combined with ganciclovir revealed a further reduction in cell viability (P < .001). ZEB1 knock-down induced cell apoptosis and the up-regulation of caspase 3 and poly(adenosine diphosphate-ribose) polymerase cleavage. Conversely, ectopic overexpression of ZEB1 in a lytic EBV-infected gastric cancer cell line (AGS-EBV) inhibited BZLF1 promoter (Zp) activity, BZLF1 expression, and apoptosis and promoted cell growth. EBV infection was detected in 11.3% (80 of 711) of gastric cancers. The presence of EBV was associated with age, men, and intestinal type cancer. CONCLUSIONS: ZEB1 was confirmed as a key mediator of the latent-lytic switch of EBV-associated gastric cancer, a distinct subtype with different clinicopathologic features. The current results indicated that inhibition of ZEB1 may be a potential target for EBV-associated gastric cancer therapy.
BACKGROUND: The role of Epstein-Barr virus (EBV) infection in gastric carcinogenesis remains largely unknown. The authors studied the effects of zinc finger E-box binding factor 1 (ZEB1) on latent-lytic switch of EBV infection in gastric cancer and explored the importance of EBV in gastric carcinogenesis. METHODS: Loss or gain of ZEB1 function was obtained by ZEB1 small-interfering RNA (siRNA) knock-down or forced ZEB1 re-expression. Cell growth was evaluated by cell viability and colony formation assays, and the cell cycle was assessed by flow cytometry. EBV was detected using quantitative polymerase chain reaction (PCR) and in situ hybridization analyses. RESULTS:ZEB1 knock-down in a latent EBV-infected gastric cancer cell line (YCC10) increased lytic gene BamHI W leftward reading frame 1 (BZLF1) expression and decreased the expression of latent gene EB nuclear antigen 1 (EBNA1) concomitant with the inhibition of cell viability (P < .05) and S-phase DNA synthesis (P < .01). ZEB1 depletion combined with ganciclovir revealed a further reduction in cell viability (P < .001). ZEB1 knock-down induced cell apoptosis and the up-regulation of caspase 3 and poly(adenosine diphosphate-ribose) polymerase cleavage. Conversely, ectopic overexpression of ZEB1 in a lytic EBV-infected gastric cancer cell line (AGS-EBV) inhibited BZLF1 promoter (Zp) activity, BZLF1 expression, and apoptosis and promoted cell growth. EBV infection was detected in 11.3% (80 of 711) of gastric cancers. The presence of EBV was associated with age, men, and intestinal type cancer. CONCLUSIONS:ZEB1 was confirmed as a key mediator of the latent-lytic switch of EBV-associated gastric cancer, a distinct subtype with different clinicopathologic features. The current results indicated that inhibition of ZEB1 may be a potential target for EBV-associated gastric cancer therapy.
Authors: Olga Speck; Weihua Tang; Douglas R Morgan; Pei Fen Kuan; Michael O Meyers; Ricardo L Dominguez; Enrique Martinez; Margaret L Gulley Journal: Appl Immunohistochem Mol Morphol Date: 2015-10
Authors: J F M Almeida; A H Campos; M A Marcello; N E Bufalo; C L Rossi; L H P Amaral; A B Marques; L L Cunha; C A Alvarenga; P C Tincani; A J Tincani; L S Ward Journal: J Endocrinol Invest Date: 2017-03-08 Impact factor: 4.256
Authors: M Constanza Camargo; Chihaya Koriyama; Keitaro Matsuo; Woo-Ho Kim; Roberto Herrera-Goepfert; Linda M Liao; Jun Yu; Gabriel Carrasquilla; Joseph J Y Sung; Isabel Alvarado-Cabrero; Jolanta Lissowska; Fernando Meneses-Gonzalez; Yashushi Yatabe; Ti Ding; Nan Hu; Philip R Taylor; Douglas R Morgan; Margaret L Gulley; Javier Torres; Suminori Akiba; Charles S Rabkin Journal: Int J Cancer Date: 2013-08-28 Impact factor: 7.396
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Authors: Amanda L Treece; Daniel L Duncan; Weihua Tang; Sandra Elmore; Douglas R Morgan; Ricardo L Dominguez; Olga Speck; Michael O Meyers; Margaret L Gulley Journal: Lab Invest Date: 2016-03-07 Impact factor: 5.662
Authors: Weihua Tang; Douglas R Morgan; Michael O Meyers; Ricardo L Dominguez; Enrique Martinez; Kennichi Kakudo; Pei Fen Kuan; Natalie Banet; Hind Muallem; Kimberly Woodward; Olga Speck; Margaret L Gulley Journal: Infect Agent Cancer Date: 2012-08-28 Impact factor: 2.965