LKB1 expression reverses the tumorigenicity of L02 cells

Abstract

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 tumorinitiating 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.

CACYBP Enhances Cytoplasmic Retention of P27Kip1 to Promote Hepatocellular Carcinoma Progression in the Absence of RNF41 Mediated Degradation

“…The results from the in vitro assays demonstrated that CACYBP overexpression had no significant effect on the proliferation and colony formation abilities in SK-Hep-1 cells, but promoted these growth abilities in LO2 cells (Figure S2B-D). LO2 is a non-cancerous hepatic cell line, although some reported that LO2 itself could form xenograft tumors in nude mice 29, 30. However, we observed no tumor formation even at month 2 after subcutaneously injecting either LO2 control or CACYBP-overexpressing cells into NSI mice (data not shown).…”

The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis

“…The human hepatic cell line LO2 was derived from primary normal human hepatocytes and has been widely applied in human hepatocellular function studies, particularly those related to drug hepatotoxicity ( 15 , 16 ). LO2 cell line was cultivated in 1640 medium with 1% penicillin (100 units/mL)/streptomycin (100 μg/mL) and 10% FBS at 37°C in a humidified atmosphere (95%) containing 5% CO 2 .…”

Muscone Induces CYP1A2 and CYP3A4 Enzyme Expression in L02 Human Liver Cells and CYP1A2 and CYP3A11 Enzyme Expression in Kunming Mice

“…The human hepatocellular carcinoma L02 cell line was used, as it has been previously reported to express high levels of hepatic CYPs, following exposure to prototypical chemical inducers [18,21,22]. L02 cells were treated with low (10 -4 μmol/L), middle (10 -3 μmol/L), and high (10 -2 μmol/L) concentrations of muscone for 48 h and the protein was extracted as described in the Materials and Methods section.…”