Reversion and Cell Hybridization of a Dedifferentiated Rat Hepatoma Cell: Dissociation of Mechanisms Establishing the Hepatic Traits

To examine the effect of insulin on hepatocytic differentiation, we took advantage of the properties of the newly established human hepatoma BC1 cell line to maintain quiescence after confluency and to progressively acquire in culture (3 weeks after confluency) an hepatocytic phenotype, as assessed by expression of specific hepatic genes (Le Jossicet al., 1995). In BC1 cells cultured in the presence of insulin (1 μM: ), expression of albumin and transferrin mRNA and protein occurs earlier than in cells cultured in its absence (1 weekvs 2 weeks). Moreover, at any time considered, the level of the two hepatic markers was higher (2- to 3-fold) in the former than in untreated cells. The beneficial effect of insulin on hepatocytic differentiation of BC1 cells was paralleled by: i) modest increases in insulin receptor (IR) mRNA level and IR binding activity, and ii) a 6-fold increase in sensitivity to insulin for stimulation of glycogenesis. These results provide the first evidence for insulin's ability to exert a positive effect on hepatocytic differentiation. The beneficial effect of insulin probably results both from increased IR expression and binding activity and from alteration at post-receptor levels.

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Evidence for a role of insulin in hepatocytic differentiation of human hepatoma BC1 cells

Kang-Park

Capeau

Munier

et al. 1995

Endocr

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An ataxia telangiectasia model: inefficient cell differentiation and possible reversal by serine protease inhibitors, tumor necrosis factor inhibitors, dexamethasone, and glutathione enhancers

Knittweis

1998

Medical Hypotheses

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The inductive effect of a human DNA sequence (HALF1) on the differentiation of a variant rat hepatoma cell (C2) is restricted to episomal forms of the molecule

Maigne

Deschatrette

1995

Journal of Cell Science

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HALF1, a 4.3 kb human DNA sequence, was originally identified as a double-stranded, closed-circular DNA molecule in revertants from a dedifferentiated rat hepatoma cell (C2) transfected with human liver DNA. Here we report its specific properties in inducing the transition to the hepatic phenotype. (i) In vitro recircularized HALF1 induces reversion after a minimum time lag of 7 days post-transfection. (ii) After induction, the presence of HALF1 is not required for maintaining the induced hepatic state. (iii) HALF1 is detected as a sequence integrated in high molecular mass DNA of human liver. (iv) HALF1 monomer or dimer plasmid constructs do not induce reversion when integrated into the genome of transfectants. (v) Short ubiquitous RNA transcripts (approximately 400 bases) are detected with specific HALF1 probes. These results indicate that the reversion process is linked to the presence of HALF1 extrachromosomal molecules.

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Reversion and Cell Hybridization of a Dedifferentiated Rat Hepatoma Cell: Dissociation of Mechanisms Establishing the Hepatic Traits

Cited by 4 publications

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Evidence for a role of insulin in hepatocytic differentiation of human hepatoma BC1 cells

Evidence for a role of insulin in hepatocytic differentiation of human hepatoma BC1 cells

An ataxia telangiectasia model: inefficient cell differentiation and possible reversal by serine protease inhibitors, tumor necrosis factor inhibitors, dexamethasone, and glutathione enhancers

The inductive effect of a human DNA sequence (HALF1) on the differentiation of a variant rat hepatoma cell (C2) is restricted to episomal forms of the molecule

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