(HEPATOLOGY 2012;56:1015–1024) Hepatocellular Neratinib purchase carcinoma (HCC) is one of the most common human cancers worldwide, particularly in Southeast Asia.1, 2 Considering the poor prognosis and high mortality of HCC, it is imperative to understand the molecular mechanisms that trigger the progression and development of HCC. Nevertheless, the exact molecular mechanisms involved in HCC are not completely

understood. Chronic infection of hepatitis B virus (HBV) is a major risk factor for HCC development.3 The HBV genome is a partial double-stranded DNA that contains four open reading frames encoding virus envelope, core protein, virus polymerase, and HBV X protein (HBx).4 Increasing evidence suggests that HBx plays an important role in hepatocarcinogenesis.3 Although HBx does not bind to DNA directly, as a multifunctional regulator, it modulates the transcription of a large number of cellular genes involved in cell survival and apoptosis by interacting with the components of signal pathways as well as the degradation

of various proteins by interacting with components of the ubiquitin (Ub)/proteasome system.5 For instance, it has been shown that HBx up-regulates the expression of several genes, such as c-jun and c-fos,6 LY294002 supplier and enhances the stability of ASC-2, c-Myc, and pituitary tumor transforming gene-1.7-9 In addition, HBx has been shown to promote the activation of several transcription factors, such as activator protein-1 (AP-1),10, 11 nuclear factor kappa light-chain enhancer of activated B cells (NF-κB),11, 12 androgen receptor (AR),13 and activating transcription factor/cyclic adenosine monophosphate–responsive element-binding transcription factor.14 Amplified in breast cancer 1 (AIB1/steroid receptor coactivator [SRC]-3/translocation-associated membrane protein-1/activator of thyroid hormone and retinoid receptor/CBP-interacting

protein/receptor-associated coactivator-3) is a member of the p160 family, which also includes SRC-1 (nuclear receptor coactivator-1) and SRC-2 (trancsiptional interacting factor 2/glucocorticoid receptor interacting protein 1).15 It has been reported that AIB1 is amplified and overexpressed in several human cancers, such as breast, mammary, prostate, stomach, colon, lung, and pancreatic cancers.15 AIB1 has been selleckchem shown to enhance the transactivation activity of some nuclear receptors, such as AR and estrogen receptor (ER), as well as a variety of transcription factors, such as AP-1 and NF-κB.15 Moreover, increasing evidence indicates that AIB1 is a bona fide oncogene that activates several signaling pathways, such as v-akt murine thymoma viral oncogene homolog (Akt), E2F1, NF-κB, HER2/neu, ERα, AR, and epidermal growth factor receptor, to promote cancer progression.15, 16 Recently, we reported that AIB1 protein is overexpressed in 68% of human HCC specimens and promotes HCC progression by enhancing cell proliferation and invasiveness.