Gene Expression in Hepatocyte-Like Lines Established by Targeted Carcinogenesis in Transgenic Mice

Exp Cell Res. 1992 May;200(1):175-85. doi: 10.1016/s0014-4827(05)80086-2.

Abstract

New hepatocyte-like cell lines (mhAT) were derived from the liver of a transgenic mouse expressing SV40 early genes under the direction of the liver-specific antithrombin III gene promoter (ATIII-TSV40). Their differentiated phenotypes were improved and stabilized by the use of liver-specific growth media (arginine-free, glucose-free, or low-fructose/glucose-free medium). The best differentiated lines display a very high level of albumin, transferrin, and L-type pyruvate kinase (L-PK) gene expression that is comparable to that observed in the mouse liver. Abundance of the aldolase B and phosphoenolpyruvate carboxykinase (PEPCK) transcripts varied from 5 to 35% of the in vivo concentrations while abundance of the alpha-fetoprotein and phenylalanine hydroxylase transcripts remained very low. Hormonal (cAMP and insulin) and nutritional (glucose) gene controls of PEPCK and L-PK were, at least partially, conserved. mhAT cells are readily transfectable by the calcium phosphate coprecipitation technique and exhibit a liver-specific pattern of expression of exogenous genes. Thus, mhAT cells seem suitable for the analysis of the regulatory regions involved in the tissue-specific transcription of genes. This work demonstrates, therefore, the great efficiency of targeted carcinogenesis in transgenic mice to create new differentiated cell lines. The availability of various lines of liver-specific cells with different phenotypes will constitute useful tools to establish correlations between expression of trans-acting factors and control of the phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / analysis
  • Animals
  • Antigens, Viral, Tumor / genetics
  • Cell Line / metabolism*
  • Gene Expression Regulation*
  • Liver / metabolism*
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Promoter Regions, Genetic
  • Pyruvate Kinase / genetics
  • RNA, Messenger / analysis
  • Trans-Activators
  • Transfection
  • Transferrin / analysis
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / analysis

Substances

  • Albumins
  • Antigens, Viral, Tumor
  • RNA, Messenger
  • Trans-Activators
  • Transferrin
  • alpha-Fetoproteins
  • Pyruvate Kinase
  • Phosphoenolpyruvate Carboxykinase (GTP)