Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin IIISV40 T large antigen transgenic mice

We have used a transgenic animal model, which constitutively develops hepat ocarcinoma (Antithrombin III SV40 T large Antigen: ASV), to study the invol vement of Annexin 1 (ANX1) in liver regeneration and malignant transformati on. Primary hepatocytes isolated from normal mice did not express ANX1. In contrast, ANX1 was strongly expressed in hepatocytes of transgenic mice dur ing 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 phosphorylati on. This upregulation correlated with increased synthesis of EGF and conseq uently with increased phosphorylation of the EGF receptor (EGF-R), Stable t ransfection of a hepatocyte cell line derived from ASV transgenic mice (mhA T2) with antisense complementary DNA for ANX1 reduced the proliferation rat e as well as cytosolic phospholipase A(2) (cPLA(2)) activity. Thus, ANX1 ex pression and phosphorylation could be a factor implicated in liver regenera tion and tumorigenesis, either through modulation of cPLA(2) activity or EG F-R function.