title: LKB1 expression reverses the tumorigenicity of L02 cells.
abstract: The tumor-suppressor liver kinase B1 (LKB1), a highly conserved and ubiquitously expressed protein kinase, plays a critical role in tumorigenesis. In the present study, we revealed that human hepatic L02 cells had severely impaired endogenous LKB1 expression as gauged by western blot, northern blot and RT-PCR analyses. Stable ectopic expression of LKB1 in L02 cells resulted in decreased cell growth, hypophosphorylation of Rb, and marked attenuation of colony formation on soft agar. Inoculation of L02 cells into immunocompromised mice resulted in the development of subcutaneous tumors, which could be completely abrogated by ectopic LKB1 expression. The tumors that formed in the mouse model recapitulated the histopathological features of hepatocellular carcinoma under the microscope. Our results jointly suggest that severely compromised endogenous LKB1 expression in the L02 cell line may confer to L02 cells tumor-initiating capacities in vivo and in vitro, and ectopic LKB1 expression antagonizes the tumorigenic properties of L02 cells. Our findings imply that caution may be needed to interpret the results obtained on the widely used human hepatic L02 cell line. The L02 cell line may be a new model to define the cellular mechanisms of liver transformation, and to unravel the molecular mechanisms underlying the growth suppressive effect of LKB1.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Tao
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases