Plasma-protein production by rat hepatoma cells in culture, their variants and revertants

Cassio, Doris; Rogier, Edith; Feldmann, Gérard; Weiss, Mary C.

doi:10.1111/j.1432-0436.1986.tb00784.x

Cited by 20 publications

(14 citation statements)

References 46 publications

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“…The results concerning AFP gene expres sion in the different hepatoma cell lines ob tained in our study confirm and extend at the mRNA level those previously described by Cassio et al [25] and Bouma et al [26]. We show that the AFP gene is strongly expressed at the mRNA and the protein level by all cells of the 7777 and HepG2 cell lines, while only a small cell percentage in the C2Rev7 cell line expresses AFP mRNA and protein.…”

Section: Discussionsupporting

confidence: 80%

“…We used three rat hepatoma cell lines (Morris hepatoma 7777, Fao and C2Rev7) and one human hepatoma cell line (HepG2). In 7777 and HepG2 cell lines all the cells strongly synthesize AFP, while in C2Rev7 cell line only a small cell percentage, and in Fao cell line no cells synthesize AFP [25,26]. We have analyzed the expression of the AFP gene and of the three nuclear oncogenes in the dif ferent hepatoma cell lines at the mRNA level using the Northern blot, the dot blot and the in situ hybridization techniques, and at the protein level by immunocytochemistry.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Oncogenes and Alpha-Fetoprotein Gene Expression in Hepatoma Cell Lines

Tournier-Thurneyssen

Feldmann

Bernuau³

1993

Tumor Biol

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We have previously demonstrated a correlation between the kinetics of activation of the nuclear oncogenes c-fos, c-jun and c-myc and the α-fetoprotein (AFP) gene in adult rat hepatocytes proliferating in culture, which led us to raise the hypothesis of a possible regulation of the AFP gene by nuclear oncogenes. Whether the mechanisms of AFP gene expression in normal and transformed hepatocytes are similar is unknown. In this study we have searched for a possible correlation between the basal level of AFP gene expression, by several hepatoma cell lines that express the AFP gene differently, and the basal level of expression of the nuclear oncogenes c-fos, c-jun and c-myc. The analysis has been performed at the mRNA and protein levels. Our results demonstrate that cell lines that strongly express the AFP gene do not express higher levels of nuclear oncogenes than cell lines with weak expression of the AFP gene. These results, therefore, do not support a direct involvement of nuclear oncogenes on the basal level of AFP gene expression in hepatoma cell lines.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Nuclear Oncogenes and Alpha-Fetoprotein Gene Expression in Hepatoma Cell Lines

Tournier-Thurneyssen

Feldmann

Bernuau³

1993

Tumor Biol

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“…Dedifferentiated hepatoma cells derived from the H4IIEC3 fail to express the majority of hepatic genes, including trans-acting factors HNF4 and HNF1␣ Cassio et al, 1986;Cereghini et al, 1990;Chin and Fournier, 1987;Weiss, 1974, 1975). Attempts to identify the mechanisms responsible for hepatic gene silencing in these cells have been unsuccessful, possibly due to the defects being multigenic.…”

Section: Introductionmentioning

confidence: 97%

Rescue of the HNF4 → HNF1α Pathway in Hepatoma Variant Cells Containing Human Chromosome 12

et al. 1998

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“…One approach to the identification of such new activators or silencers of hepatic differentiation consists of a phenotypic characterization of cells of common origin that do and do not display a dissociation between expression of the LETF and their target functions. In the extensively characterized rat hepatoma H4IIEC3 cell system, appropriate cell lines to search for such a dissociation turned out to be morphologically heterogeneous variants, previously designated as unstable (11,23,59). Moore and Weiss (59) demonstrated that certain of these clonal variants selected from differentiated hepatoma cells can give rise to both dedifferentiated and differentiated progeny clones.…”

mentioning

confidence: 99%

Liver-Enriched Transcription Factors Uncoupled from Expression of Hepatic Functions in Hepatoma Cell Lines

Chaya

Fougère-Deschatrette

Weiss

1997

Molecular and Cellular Biology

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Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver.Genetic analysis of hepatoma-derived cell lines revealed, many years ago, that expression of differentiated functions is regulated in trans by mechanisms whose final effects are negative (extinction) or positive (activation) (78). More recent studies of these hepatoma lines further showed that maintenance of the hepatic phenotype is an active process operating at the level of transcription (21,42). By analysis of DNA sequences implicated in liver-specific transcription, the identification and cloning of members of four major families of liverenriched transcription factors (LETF) have been achieved. These families, each characterized by structurally related DNA binding domains, include the hepatocyte nuclear factor families HNF1, HNF3, and HNF4 and the CCAAT enhancer binding protein (C/EBP) family (13,82). Determination of the tissue distribution of these factors and analysis of their hierarchical relations led to the hypothesis that the combinatorial action of LETF together with the ubiquitous transcriptional machinery of the cell is necessary and maybe even sufficient for the maintenance of liver-specific gene transcription (30, 81). Indeed, the H4IIEC3 differentiated rat hepatoma cells and their derivatives that stably express an extensive set of adult hepatic functions express all the LETF identified to date, while in the rare dedifferentiated rat hepatoma cells that have lost expression of all these hepatic functions, HNF4 and HNF1 are systematically absent. In addition,...

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Plasma-protein production by rat hepatoma cells in culture, their variants and revertants

Cited by 20 publications

References 46 publications

Nuclear Oncogenes and Alpha-Fetoprotein Gene Expression in Hepatoma Cell Lines

Nuclear Oncogenes and Alpha-Fetoprotein Gene Expression in Hepatoma Cell Lines

Rescue of the HNF4 → HNF1α Pathway in Hepatoma Variant Cells Containing Human Chromosome 12

Liver-Enriched Transcription Factors Uncoupled from Expression of Hepatic Functions in Hepatoma Cell Lines

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