title: Progression of liver oncogenesis in the double transgenic mice c-myc/TGF α is not enhanced by cyclooxygenase-2 expression.
abstract: Cyclooxygenase-2 (COX-2) has been associated with cell growth regulation, tissue remodeling and carcinogenesis. Overexpression of COX-2 in hepatocytes constitutes an ideal condition to evaluate the role of prostaglandins (PGs) in liver pathogenesis. The effect of COX-2-dependent PGs in genetic hepatocarcinogenesis has been investigated in triple c-myc/transforming growth factor α (TGF-α) transgenic mice that express human COX-2 in hepatocytes on a B6CBAxCD1xB6DBA2 background. Analysis of the contribution of COX-2-dependent PGs to the development of hepatocarcinogenesis, evaluated in this model, suggested a minor role of COX-2-dependent prostaglandins to liver oncogenesis as indicated by liver histopathology, morphometric analysis and specific markers of tumor progression. This allows concluding that COX-2 is insufficient for modifying the hepatocarcinogenesis course mediated by c-myc/TGF-α.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM Madrid, Arturo Duperier, 4, 28029 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Llorente-Izquierdo
authors.forename: Rafael
authors.initials: R
authors.lastname: Mayoral
authors.forename: Carme
authors.initials: C
authors.lastname: Cucarella
authors.forename: Carlos
authors.initials: C
authors.lastname: Grau
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Alvarez
authors.forename: Juana María
authors.initials: JM
authors.lastname: Flores
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Palencia
authors.forename: Noelia
authors.initials: N
authors.lastname: Agra
authors.forename: Luis
authors.initials: L
authors.lastname: Castro-Sánchez
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín-Sanz
authors.forename: Marta
authors.initials: M
authors.lastname: Casado
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016211:Transforming Growth Factor alpha; D051546:Cyclooxygenase 2
keywords: Biomarkers; COX-2; HCC; PGE(2); Transgenic mice; c-myc/TGF-α model