title: Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells.
abstract: Hepatocellular carcinoma (HCC) is a malignant tumor and hepatitis B virus X protein (HBx) plays a crucial role in its pathogenesis. The Notch1 signaling pathway is involved in various malignant tumors including liver cancers and down-regulation of Notch-1 may exert anti-tumor effects. Here, we demonstrate that inhibition of Notch1 by plasmid-based shRNA suppresses growth of human hepatic cells transfected with HBx through G0/G1 cell cycle arrest and apoptosis inhibition, possibly linked to the promoted expression of cyclin-dependent kinase inhibitor, P16, and decreased expression of apoptosis inhibitor, Bcl-2. The anti-proliferative and pro-apoptotic effects of Notch1 shRNA in HBx-transformed L02 cell may be partly mediated by down-regulation of nuclear factor-kappaB (NF-κB) binding activities, demonstrating possible cross-talk between Notch-1 and NF-κB signaling pathways. The oncogene HBx may therefore induce malignant transformation of human hepatic cells via Notch1 pathway, indicating that Notch1 plays a crucial role in HBx-related liver cancer and could be an effective therapeutic target for HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xia
authors.forename: Jinling
authors.initials: J
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Luo
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497761:NOTCH1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein