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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalBiochemical Engineering Journal
Volume60
DOIs
Publication statusPublished - Jan 15 2012

Fingerprint

Transcription factors
Liver
Hepatocellular Carcinoma
Transcription Factors
CCAAT-Enhancer-Binding Proteins
Hepatocyte Nuclear Factor 1
Genes
Hepatocyte Nuclear Factor 6
Clone cells
Hepatocyte Nuclear Factor 4
Hepatocyte Nuclear Factors
Artificial Liver
Cell proliferation
Transcription
Hepatocytes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Environmental Engineering
  • Biomedical Engineering

Cite this

@article{80c1c4e210154175bd7388c3d0b00184,
title = "Enhanced liver functions in mouse hepatoma cells by induced overexpression of liver-enriched transcription factors",
abstract = "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.",
author = "Hideaki Yamamoto and Kawabe Yoshinori and Akira Ito and Masamichi Kamihira",
year = "2012",
month = "1",
day = "15",
doi = "10.1016/j.bej.2011.10.004",
language = "English",
volume = "60",
pages = "67--73",
journal = "Biochemical Engineering Journal",
issn = "1369-703X",
publisher = "Elsevier",

}

TY - JOUR

T1 - Enhanced liver functions in mouse hepatoma cells by induced overexpression of liver-enriched transcription factors

AU - Yamamoto, Hideaki

AU - Yoshinori, Kawabe

AU - Ito, Akira

AU - Kamihira, Masamichi

PY - 2012/1/15

Y1 - 2012/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=83555176233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83555176233&partnerID=8YFLogxK

U2 - 10.1016/j.bej.2011.10.004

DO - 10.1016/j.bej.2011.10.004

M3 - Article

VL - 60

SP - 67

EP - 73

JO - Biochemical Engineering Journal

JF - Biochemical Engineering Journal

SN - 1369-703X

ER -