ENHANCED EXPRESSION OF THE PROTEIN-KINASE SUBSTRATE ANNEXIN-I IN HUMAN HEPATOCELLULAR-CARCINOMA

Annexin (AX) constitutes a new family of Ca2+-dependent membrane-bindi ng proteins; 13 of them have been described, Among these, annexin-I (A X-I) has displayed many biological functions in vitro, Its actual role in vivo however, remains unknown. We already reported that AX-I was e xpressed in proliferating (regenerating) hepatocytes at both protein a nd messenger RNA (mRNA) levels, The role of AX-I in human hepatocellul ar carcinoma (HCC) remains obscure. In this study, the amounts of AX-I at protein and mRNA levels, as well as its localization, have been de termined in the normal human liver, chronic hepatitis Liver, and nontu morous and tumorous portions of HCC. AX-I was rarely found in normal a nd chronic liver tissues, whereas it is overexpressed at both the tran scriptional and translational levels in tumorous and nontumorous regio ns of HCC, In addition, more AXI was expressed in the tumorous portion than the nontumorous portion of HCC. AX-I was present in the hepatocy tes and HCC cells, localized mainly in the cytoplasm, AX-I was overexp ressed in poorly differentiated cancer cells, Furthermore, AX-I was ty rosine-phosphorylated in HCC, We also found that some of the AX-I-posi tive hepatocytes in the nontumorous tissues were derived from a partic ular subset of parenchymal cells (stem or oval cells). These results i ndicate that AX-I plays an important role in the malignant transformat ion process leading to HCC and that it is closely related to the histo logical grade of HCC, HCC would offer a novel tool with which to study the function of AX-I in malignant transformation.