| Autor: |
Liu Y; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.; Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China., Li YQ; Department of Hematology, Central Hospital of Xuhui District, Shanghai 200030, China., Huang SH; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Li YL; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.; Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China., Xia JW; The Third People's Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China., Jia JS; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Wei F; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Wang JH; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Dai GQ; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Wang YC; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China., Li XY; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.; Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China., Han LX; The Third People's Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China., Zhang XL; Department of Physiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China., Xiang XD; Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming 650118, China., Zhao WT; Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming 650118, China., Xiao D; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.; Institute of Comparative Medicine and Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China., Lin XL; Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China. |
| Abstrakt: |
In this study, we investigated the role of embryonic gene Cripto-1 (CR-1) in hepatocellular carcinoma (HCC) using hepatocyte-specific CR-1-overexpressing transgenic mice. The expression of truncated 1.7-kb CR-1 transcript (SF-CR-1) was significantly higher than the full-length 2.0-kb CR-1 transcript (FL-CR-1) in a majority of HCC tissues and cell lines. Moreover, CR-1 mRNA and protein levels were significantly higher in HCC tissues than adjacent normal liver tissues. Hepatocyte-specific over-expression of CR-1 in transgenic mice enhanced hepatocyte proliferation after 2/3 partial hepatectomy (2/3 PHx). CR-1 over-expression significantly increased in vivo xenograft tumor growth of HCC cells in nude mice and in vitro HCC cell proliferation, migration, and invasion. CR-1 over-expression in the transgenic mouse livers deregulated HCC-related signaling pathways such as AKT, Wnt/β-catenin, Stat3, MAPK/ERK, JNK, TGF-β and Notch, as well as expression of HCC-related genes such as CD5L, S100A8, S100A9, Timd4, Orm2, Orm3, PDK4, DMBT1, G0S2, Plk2, Plk3, Gsta1 and Gsta2 . However, histological signs of precancerous lesions, hepatocyte dysplasia or HCC formation were not observed in the livers of 3-, 6- or 8-month-old hepatocyte-specific CR-1-overexpressing transgenic mice. These findings demonstrate that liver-specific CR-1 overexpression in transgenic mice deregulates signaling pathways and genes associated with HCC. |
