Enhanced expression of the protein kinase substrate annexin in human hepatocellular carcinoma

Abstract

Annexin (AX) constitutes a new family of Ca2+-dependent membrane-binding proteins; 13 of them have been described. Among these, annexin-1 (AX-I) has displayed many biological functions in vitro. Its actual role in vivo, however, remains unknown. We already reported that AX-I was expressed in proliferating (regenerating) hepatocytes at both protein and messenger RNA (mRNA) levels. The role of AX-I in human hepatocellular carcinoma (HCC) remains obscure. In this study, the amounts of AX-I at protein and mRNA levels, as well as its localization, have been determined in the normal human liver, chronic hepatitis liver, and nontumorous and tumorous portions of HCC. AX-I was rarely found in normal and chronic liver tissues, whereas it is overexpressed at both the transcriptional and translational levels in tumorous and nontumorous regions of HCC. In addition, more AX-I was expressed in the tumorous portion than the nontumorous portion of HCC. AX-I was present in the hepatocytes and HCC cells, localized mainly in the cytoplasm. AX-I was expressed in poorly differentiated cancer cells. Furthermore, AX-I was tyrosine-phosphorylated in HCC. We also found that some of the AX-I- positive hepatocytes in the nontumorous tissues were derived from a particular subset of parenchymal cells (stem or oval cells). These results indicate that AX-I plays an important role in the malignant transformation process leading to HCC and that it is closely related to the histological grade of HCC. HCC would offer a novel tool with which to study the function of AX-I in malignant transformation.

MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers

“…In contrast to the suppressed expression of ANXA1 observed in the above-mentioned cancers, increased ANXA1 expression has been reported in pancreatic (Bai et al, 2004), hepatic (Masaki et al, 1996), glial (Johnson et al, 1989) and stomach cancers (Sinha et al, 1998), suggesting that the functional role of ANXA1 may be tissue-and cell type-specific. These findings further highlight the complexity and highly specific nature of ANXA1 physiological functions.…”

Proteomic characterization of harvested pseudopodia with differential gel electrophoresis and specific antibodies

“…56 Immunohistochemical studies of breast and hepatocellular carcinoma also indicated that AnxI is associated with tumor progression. [57][58][59] The contribution of AnxI to pseudopodial extension during migration may explain AnxI's association with tumor progression and HGF signaling seen in other cells 18 and with activated HGF in U87 pseudopodia. Also, AnxII was previously identified more frequently in high-grade than low-grade gliomas, 50 of 65 and three of 10 tumors, respectively, following 2D electrophoresis of tissue samples.…”

Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin iii sv40 t large antigen transgenic mice

“…While we were carrying these experiments, ANX1 was reported to be strongly expressed in human hepatocellular (hcc) carcinoma cells, suggesting that its induction in the liver could be associated with malignant transformation. 4,5 We therefore addressed the question of the role of ANX1 in liver transformation.Recently, transgenic mice (ASV) expressing the SV40 early region coding for large T antigen under the control of the liver-specific human antithrombin III gene promoter have been created in our laboratory to study oncogenic transformation on hepatocyte function. 6 Phenotypically, the animals present a hepatocellular carcinoma, with a neoplasia at 3 to 9 weeks and later (after tumor development) a severe dysplasia, an augmentation of hepatocytes in S phases, an important cytolysis (necrosis), and an early apoptosis (2.5%-5%).…”

“…While we were carrying these experiments, ANX1 was reported to be strongly expressed in human hepatocellular (hcc) carcinoma cells, suggesting that its induction in the liver could be associated with malignant transformation. 4,5 We therefore addressed the question of the role of ANX1 in liver transformation.…”