Progression of liver oncogenesis in the double transgenic mice c-myc/TGF α is not enhanced by cyclooxygenase-2 expression

•We examined the role of prostaglandins in hepatocarcinogenesis in an animal model of genetically induced liver tumors.•A functional COX-2 transgene in liver did not contribute to enhanced HCC development and onset by c-myc/TGF-α.•COX-2-dependent prostaglandin synthesis in liver has a minor contribu...

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Published in:Prostaglandins & other lipid mediators 2013-10, Vol.106, p.106-115
Main Authors: Llorente-Izquierdo, Cristina, Mayoral, Rafael, Cucarella, Carme, Grau, Carlos, Alvarez, Maria Soledad, Flores, Juana María, García-Palencia, Pilar, Agra, Noelia, Castro-Sánchez, Luis, Boscá, Lisardo, Martín-Sanz, Paloma, Casado, Marta
Format: Article
Language:English
Subjects:
Animals
Biomarkers
c-myc/TGF-α model
Carcinogenesis - genetics
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
COX-2
Cyclooxygenase 2 - genetics
Disease Progression
Female
Gene Expression
HCC
Humans
Liver - metabolism
Liver - pathology
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
Mice
Mice, Transgenic
PGE2
Proto-Oncogene Proteins c-myc - genetics
Signal Transduction - genetics
Transforming Growth Factor alpha - genetics
Transgenic mice
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Summary:•We examined the role of prostaglandins in hepatocarcinogenesis in an animal model of genetically induced liver tumors.•A functional COX-2 transgene in liver did not contribute to enhanced HCC development and onset by c-myc/TGF-α.•COX-2-dependent prostaglandin synthesis in liver has a minor contribution to liver oncogenesis. 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.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2013.03.006