Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin iii sv40 t large antigen transgenic mice
Autor: | Raphaëlle Gillet, Pascale Briand, Catherine de Coupade, Françoise Russo-Marie, Egle Solito, Myriam Bennoun |
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Rok vydání: | 2000 |
Předmět: |
Genetically modified mouse
medicine.medical_specialty Carcinoma Hepatocellular Antigens Polyomavirus Transforming Transgene Antithrombin III Mice Inbred Strains Mice Transgenic Biology Malignant transformation Mice Downregulation and upregulation Annexin Internal medicine medicine Animals Hepatectomy Postoperative Period Phosphorylation Promoter Regions Genetic Cells Cultured Annexin A1 Epidermal Growth Factor Hepatology Liver Neoplasms Molecular biology Liver regeneration Liver Regeneration Up-Regulation Cell Transformation Neoplastic medicine.anatomical_structure Endocrinology Hepatocyte |
Zdroj: | Hepatology. 31:371-380 |
ISSN: | 1527-3350 0270-9139 |
DOI: | 10.1002/hep.510310217 |
Popis: | We have used a transgenic animal model, which constitutively develops hepatocarcinoma (Antithrombin III SV40 T large Antigen: ASV), to study the involvement of Annexin 1 (ANX1) in liver regeneration and malignant transformation. Primary hepatocytes isolated from normal mice did not express ANX1. In contrast, ANX1 was strongly expressed in hepatocytes of transgenic mice during constitutive development of hepatocarcinoma. In ASV transgenic mice, an elevated ANX1 level preceded the appearance of the tumor, indicating that it could be a good marker in the diagnosis of cancer. One-third hepatectomy in normal mice resulted in stimulation of ANX1 synthesis and phosphorylation. This upregulation correlated with increased synthesis of EGF and consequently with increased phosphorylation of the EGF receptor (EGF-R). Stable transfection of a hepatocyte cell line derived from ASV transgenic mice (mhAT2) with antisense complementary DNA for ANX1 reduced the proliferation rate as well as cytosolic phospholipase A(2) (cPLA(2)) activity. Thus, ANX1 expression and phosphorylation could be a factor implicated in liver regeneration and tumorigenesis, either through modulation of cPLA(2) activity or EGF-R function. |
Databáze: | OpenAIRE |
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