In addition,

the expression level of cyclin D1 was much higher in peritumor cells compared to that of tumor cells, and c-myc expression showed a similar pattern selleck screening library (Figure 4). Figure 4 Expression levels of cyclin D1 and c-myc in HCC tissues. By real-time PCR, the expression levels of LEF-1 downstream effector genes cyclin D1 (A) and c-myc (B) were compared in tumor tissues (T), peritumor tissues (pT) and normal liver tissues (NL). The expression levels of cyclin D1 and c-myc were significantly induced in tumor tissues compared to that of peritumor tissues and normal liver tissues (* p < 0.05). Discussion Hepatocellular carcinoma is the fifth most common malignancy worldwide [13]. Its risk factors include chronic infections by hepatitis B and C virus (HBV and HCV), and nonviral liver diseases [14, 15]. Epidemiological study indicated that long term persistence

of HBsAg in chronic hepatitis B patients is a risk factor for the development of HCC [7]. Extensive studies have been carried out to reveal the roles of HBV in contributing to proliferation and anti-apoptotic behavior of HCC cells [16, 17]. Cumulative data suggested that HBx is a multifunctional regulatory viral protein, which interferes directly or indirectly with a variety of cellular 4-Hydroxytamoxifen EPZ5676 order functions including cell cycle progression, transformation and apoptosis [18–20]. Other groups reported that LHBs and MHBs functioned as trans-activators which induced cell proliferation and/or cell death of hepatocytes

[21–23]. In this study we investigated the possible roles played by major HBs in tumorgenesis, selleck chemicals and the association between HBsAg expression and Wnt signaling pathway deregulation in HBV-associated HCC tissues. To reveal the implications of in vivo association between HBsAg and LEF-1 up-regulation in HCC, the expression levels of these two proteins were compared both by immunohistochemical staining and by real-time PCR among HCC tumor tissues, peritumor tissues and normal liver tissues. Experimental data have shown that the aberrant regulation of the canonical Wnt pathway was one of the important events involved in HCC development [24, 25]. However, mutations in β-catenin or adenomatous polyposis coli (APC) genes, which appeared in over 90% of colorectal cancers [26, 27] were found only in about 20–30% of HCCs [28], suggesting that the predominant mechanisms activating Wnt signaling pathway in HCCs could be different from that in other cancers. Bengochea et al reported that deregulation of Wnt/Frizzled receptor elements was common in human hepatocellular carcinoma [29], and disturbance of regulatory mechanisms other than mutations involving β-catenin is more likely of importance in HCC.