Enhanced liver functions in mouse hepatoma cells by induced overexpression of liver-enriched transcription factors

• Published in: Biochemical engineering journal Vol. 60; no. 15; pp. 67 - 73
• Main Authors: Yamamoto, Hideaki, Kawabe, Yoshinori, Ito, Akira, Kamihira, Masamichi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2012
• Subjects: Animal cell culture; binding proteins; Biomedical; carcinoma; cell proliferation; clones; gene overexpression; genes; genetic engineering; hepatocytes; hepatoma; Hepatoma cell; liver; Liver function; Liver-enriched transcription factor; mice; Recombinant DNA; retroviral vectors; support systems; transcription factors; Animal cell culture; Hepatoma cell; Liver function; Recombinant DNA; Liver-enriched transcription factor; Biomedical
• ISSN: 1369-703X; 1873-295X
• DOI: 10.1016/j.bej.2011.10.004

► Overexpression of eight liver-enriched transcription factors enabled the induction of liver functions in hepatoma cells. ► Switching between proliferation and expression of differentiated functions can be controlled in the genetically engineered hepatoma cells. ► This genetic modification approach for hepatoma cells can provide a means for generating cell sources for bioartificial liver support systems. Hepatoma cells, which are derived from liver carcinoma, are able to proliferate infinitely under culture conditions. However, the liver functions of hepatoma cells are generally low compared with those of hepatocytes in a liver. Here, we attempted to create genetically engineered hepatoma cells with enhanced liver functions by overexpression of liver-enriched transcription factors (LETFs), which are associated with the transcription of liver-specific genes and hepatic differentiation. For this purpose, genes for eight LETFs, hepatocyte nuclear factor (HNF)-1α, HNF-1β, HNF-3β, HNF-4α, HNF-6, CCAAT/enhancer binding protein (C/EBP)-α, C/EBP-β and C/EBP-γ, were obtained from the mouse liver. Mouse hepatoma Hepa1-6 cells were transduced with retroviral vectors, in which inducible expression cassettes for the LETF genes were introduced. Cell clones with inducible expression of high liver functions were established. Upon overexpression of the LETF genes, cell proliferation ceased and the cells exhibited an epithelial morphology, indicating hepatic maturation of hepatoma cells. This approach for genetic modification of hepatoma cells may be promising for the construction of cells for use in bioartificial liver support systems.