Elsevier

Developmental Biology

Volume 35, Issue 1, November 1973, Pages 83-96
Developmental Biology

Full paper
Expression of liver phenotypes in cultured mouse hepatoma cells: Synthesis and secretion of serum albumin

https://doi.org/10.1016/0012-1606(73)90008-0Get rights and content

Abstract

A permanent cell line, designated Hepa, has been isolated from a mouse hepatoma, BW 7756. The cell line synthesizes and secretes albumin at rates appreciably higher than previously reported hepatomas adapted to in vitro conditions. Monospecific antimouse serum albumin was produced in rabbits, and mouse serum albumin secreted by the hepatoma cells was identified by double diffusion, immunoelectrophoresis, and radioimmunodiffusion. A quantitative immunoassay was used to measure albumin secretion and to study the effects of culture conditions on albumin secretion. A subclonal analysis was performed to study the homogeneity and stability of cloned hepatoma lines in respect to albumin secretion. Different secretion rates were observed during the culture cycle. Significant clonal variation in respect to albumin secretion was found among ten subclones.

The significance of clonal variation is discussed in relation to the study of epigenetic control of albumin expression in somatic hybrid cells.

References (42)

  • D.M. Bissel et al.

    Morphology and function of cells of human embryonic liver in monolayer culture

    J. Cell Biol

    (1971)
  • C. Borek

    Neoplastic transformation in vitro of a clone of adult liver epithelial cells into differentiated hepatoma-like cells under conditions of nutritional stress

  • P.N. Campbell et al.

    Studies on the synthesis of serum albumin by the isolated microsome fraction from rat liver

    Biochem. J

    (1960)
  • H.G. Coon

    Clonal culture of differentiated cells from mammals: Rat liver cell culture

    Carnegie Inst. Wash. Yearb

    (1969)
  • G.J. Darlington et al.

    A murine cell line expressing liver functions in vitro

    (1973)
  • G.J. Darlington et al.

    Activation of a human differentiated phenotype (albumin synthesis) in mouse hepatoma × human leucocyte somatic cell hybrids

  • R.L. Davidson

    Regulation of gene expression in somatic cell hybrids: a review

    In Vitro

    (1971)
  • B. Ephrussi

    Hybridization of Somatic Cells

    (1972)
  • H. Glaumann et al.

    Evidence for the participation of the golgi apparatus in the intracellular transport of nascent albumin in the liver cell

    J. Cell Biol

    (1970)
  • A.H. Gordon et al.

    Methods for measuring rates of synthesis of albumin by the isolated perfused rat liver

    Biochem. J

    (1960)
  • Y. Hamashima et al.

    The localization of albumin and fibrinogen in human liver cells

    J. Cell Biol

    (1964)
  • Cited by (145)

    • Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

      2017, Toxicology and Applied Pharmacology
      Citation Excerpt :

      Error bars represent standard error of the mean (SEM). Mouse Hepa-1c1c7 cells and human HepG2 cells are commonly used in liver studies and were derived from a mouse and human hepatomas, respectively (Bernhard et al., 1973; Hankinson, 1979; Hankinson et al., 1991; Ihrke et al., 1993). The mouse H1L7.5c3 cell line variant was engineered by stable transfection of the pGudLuc7.5 plasmid into Hepa-1c1c7 cells (He et al., 2011) as was the HepG2 (40/6) cell line using pGudluc 6.1 and parental HepG2 cells (Long et al., 1998), in which both cell lines express an AHR-dependent, luciferase reporter gene system.

    • Critical Roles of the Histone Methyltransferase MLL4/KMT2D in Murine Hepatic Steatosis Directed by ABL1 and PPARγ2

      2016, Cell Reports
      Citation Excerpt :

      Second, PPARγ has been reported to directly activate the expression of at least three of our identified steatotic genes: Cd36 (Tontonoz et al., 1998), Plin2 (Fan et al., 2009; Kang et al., 2015), and Cidec (Kim et al., 2008; Matsusue et al., 2008). Third, in the mouse liver carcinoma cell line Hepa1c1c7, which has been widely utilized as a surrogate cell line to study liver biology (Bernhard et al., 1973), the expression of three of our identified steatotic genes, Scd1, Cd36, and Cidec, was induced by the PPARγ ligand rosiglitazone, and these inductions were impaired by co-transfected small hairpin RNA (shRNA) construct against MLL4 (Figure 3A). Fourth, similar inductions were also observed with livers from WT mice when 30 mg/kg of rosiglitazone was given by daily intraperitoneal injection for 7 days, whereas these hepatic inductions were significantly dampened in Mll4+/− mice (Figure 3B).

    • Liver retinol transporter and receptor for serum retinol-binding protein (RBP4)

      2013, Journal of Biological Chemistry
      Citation Excerpt :

      Nevertheless, we are able to confirm high level expression of a RBPR2-alkaline phosphatase fusion protein in the liver of RBPR2 promoter-reporter mice, confirming qRT-PCR findings that RBPR2 expression is highest in the liver. Consistent with this, RBPR2 mRNA is detected in H4IIe and Hepa1 hepatoma cells, lines known to express markers of differentiated hepatocytes (58, 59). In addition, the diffuse pattern of β-gal expression in intact liver of RBPR2 promoter-reporter mice suggests that hepatocytes, which make up 80% of liver by mass (60), are the principal cell type in which RBPR2 is expressed.

    • Transcriptional regulation of bone marrow thrombopoietin by platelet proteins

      2008, Experimental Hematology
      Citation Excerpt :

      To investigate the role that soluble products of platelet release or blood coagulation might play in the regulation of TPO expression, cultured primary murine bone marrow stromal cells and model stromal cell lines were treated with varying concentrations of normal serum. OP9 cells were selected as a model of bone marrow stromal cells based on their ability to support the in vitro differentiation of ES cells toward hematopoietic lineages [13]. The murine hepatoma–derived cell line, Hepa1c1c7, was selected to represent liver cells.

    • Alternative invasion pathways for plasmodium berghei sporozoites

      2007, International Journal for Parasitology
    View all citing articles on Scopus

    This study was supported by NIH grant USPHS 5-R01-BM 09966 and NSF grant GB 34303, and a postdoctoral fellowship from the Swiss National Science Foundation (awarded to H.P.B.).

    View full text