TY - JOUR
T1 - Phenotypic characterization of rat hepatoma cell lines and lineage-specific regulation of gene expression by differentiation agents
AU - Zvibel, Isabel
AU - Fiorino, Anthony S.
AU - Brill, Shlomo
AU - Reid, Lola M.
N1 - Funding Information:
&p.2: wledgements I. Zvibel and A. Fiorino contributed equally to the discussions and writing process through which this article developed. These studies were supported by an American Cancer Society grant (BE-92 C), an NIH grant (DK44266), and a grant from The Council for Tobacco Research (1897 A and 1897B). Shlomo Brill received support from the Department of Molecular Pharmacology, The Richard Molin Foundation, and by an American Physician’s Fellowship. Salary support for Anthony S. Fiorino derived from an NIH M.S.T.P. grant (5T32-GM07288; Betty Diamond, PI). We wish to thank Dinish Williams for technical support, Patricia Holst for laboratory management, and Rosina Pas-sela for secretarial assistance.
PY - 1998
Y1 - 1998
N2 - Hepatoma cell lines can be characterized by their expression of hepatocyte- and biliary-specific genes and by their response to differentiating agents in a lineage-dependent manner. These characteristics can be used to map the maturational lineage position of the cell lines. Tissue-specific gene expression and regulation by heparin, dimethylsulfoxide (DMSO), and sodium butyrate (SB) were examined in three rat hepatoma cell lines and two rat liver epithelial cell lines. Based on antigenic profiles and gene expression in serum-supplemented medium, the hepatoma cell lines could be organized in distinct categories of hepatic differentiation. All three hepatomas expressed the following five genes: γ-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and α5 and β1 integrin. Cell line H4AzC2 also expressed α-fetoprotein (AFP), albumin, IGF II receptor, and the biliary/oval cell antigens OC.2 and OC.3, a phenotype characteristic of fetal hepatocytes. FTO-2B cells lacked AFP, OC.2, and OC.3 but expressed albumin and IGF II receptor in addition to the five commonly expressed genes, consistent with a more hepatocyte-like phenotype. Cell line H5D.7 expressed neither albumin nor the IGF II receptor, but did express OC.2, OC.3, and α3 integrin in addition to the five commonly expressed genes, characteristic of biliary epithelial cells. Regulation of gene expression by heparin, DMSO, and SB was examined in cells cultured in hormonally defined medium. The patterns of regulation of AFP, albumin, GGT, and Yp were dependent upon the state of differentiation of the cell. FTO-2B cells regulated genes in a manner similar to that of E16 fetal hepatocytes, H4AzC2 regulated genes characteristic of both hepatocytic and biliary lineages, and H5D.7 regulated only biliary genes. Suppression of GGT by DMSO was uniformly observed. The three cell lines expressed equal amounts of HNF-4, but FTO-2B cells expressed more HNF-3β and less HNF-3α, while the reverse was true of H4AzC2 and H5D.7 cells.
AB - Hepatoma cell lines can be characterized by their expression of hepatocyte- and biliary-specific genes and by their response to differentiating agents in a lineage-dependent manner. These characteristics can be used to map the maturational lineage position of the cell lines. Tissue-specific gene expression and regulation by heparin, dimethylsulfoxide (DMSO), and sodium butyrate (SB) were examined in three rat hepatoma cell lines and two rat liver epithelial cell lines. Based on antigenic profiles and gene expression in serum-supplemented medium, the hepatoma cell lines could be organized in distinct categories of hepatic differentiation. All three hepatomas expressed the following five genes: γ-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and α5 and β1 integrin. Cell line H4AzC2 also expressed α-fetoprotein (AFP), albumin, IGF II receptor, and the biliary/oval cell antigens OC.2 and OC.3, a phenotype characteristic of fetal hepatocytes. FTO-2B cells lacked AFP, OC.2, and OC.3 but expressed albumin and IGF II receptor in addition to the five commonly expressed genes, consistent with a more hepatocyte-like phenotype. Cell line H5D.7 expressed neither albumin nor the IGF II receptor, but did express OC.2, OC.3, and α3 integrin in addition to the five commonly expressed genes, characteristic of biliary epithelial cells. Regulation of gene expression by heparin, DMSO, and SB was examined in cells cultured in hormonally defined medium. The patterns of regulation of AFP, albumin, GGT, and Yp were dependent upon the state of differentiation of the cell. FTO-2B cells regulated genes in a manner similar to that of E16 fetal hepatocytes, H4AzC2 regulated genes characteristic of both hepatocytic and biliary lineages, and H5D.7 regulated only biliary genes. Suppression of GGT by DMSO was uniformly observed. The three cell lines expressed equal amounts of HNF-4, but FTO-2B cells expressed more HNF-3β and less HNF-3α, while the reverse was true of H4AzC2 and H5D.7 cells.
UR - http://www.scopus.com/inward/record.url?scp=0031652740&partnerID=8YFLogxK
U2 - 10.1111/j.1432-0436.1998.00215.x
DO - 10.1111/j.1432-0436.1998.00215.x
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C2 - 9745712
AN - SCOPUS:0031652740
SN - 0301-4681
VL - 63
SP - 215
EP - 223
JO - Differentiation
JF - Differentiation
IS - 4
ER -