Annexins (ANXs) constitute a family of Ca2+-
dependent membrane-binding proteins; at least 20 of them
have been described to date. Among these, Annexin A2
(ANXA2) has been revealed as a multi-functional protein
in vitro. Its actual role in vivo, however, requires further
investigation. We already reported that ANX-I (ANXA1)
was up-regulated in hepatocellular carcinoma (HCC). The
role of ANXA2 in various liver diseases including HCC
remains obscure. In the present study, the protein and
mRNA levels of ANXA2, as well as its localization, were
determined for the normal human liver, chronic hepatitis
liver, and non-tumorous and tumorous portions of HCC
tissues. ANXA2 was rarely detected in either normal or
chronic hepatitis liver tissues, whereas it was overexpressed
at both the transcriptional and translational levels in tumorous
and non-tumorous regions of HCC. In addition, in many
cases, more ANXA2 was expressed in the tumorous portion
than in the non-tumorous portion of HCC. The expression
of ANXA2 was mainly localized in cancer cells, especially
in poorly differentiated HCC. Furthermore, ANXA2 was
tyrosine-phosphorylated in HCC. These data suggest that
overexpression and tyrosine phosphorylation of ANXA2
play important roles in the malignant transformation process
leading to HCC and are related to the histological grade of