Zvibel I, Fiorino A S, Brill S, Reid L M
Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Israel.
Differentiation. 1998 Aug;63(4):215-23. doi: 10.1111/j.1432-0436.1998.00215.x.
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: gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and alpha 5 and beta 1 integrin. Cell line H4AzC2 also expressed alpha-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 alpha 3 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-3 beta and less HNF-3 alpha, while the reverse was true of H4AzC2 and H5D.7 cells.
肝癌细胞系可通过其肝细胞和胆管特异性基因的表达以及它们对分化剂的谱系依赖性反应来表征。这些特征可用于确定细胞系的成熟谱系位置。在三种大鼠肝癌细胞系和两种大鼠肝上皮细胞系中检测了组织特异性基因表达以及肝素、二甲基亚砜（DMSO）和丁酸钠（SB）对其的调节作用。基于血清补充培养基中的抗原谱和基因表达，肝癌细胞系可分为不同的肝分化类别。所有三种肝癌细胞系均表达以下五个基因：γ-谷氨酰转肽酶（GGT）、谷胱甘肽-S-转移酶π（Yp）、谷氨酰胺合成酶以及α5和β1整合素。细胞系H4AzC2还表达甲胎蛋白（AFP）、白蛋白、胰岛素样生长因子II受体以及胆管/卵圆细胞抗原OC.2和OC.3，这是胎儿肝细胞的一种表型特征。FTO-2B细胞缺乏AFP、OC.2和OC.3，但除了五个共同表达的基因外，还表达白蛋白和胰岛素样生长因子II受体，这与更类似肝细胞的表型一致。细胞系H5D-7既不表达白蛋白也不表达胰岛素样生长因子II受体，但除了五个共同表达的基因外，还表达OC.2、OC.3和α3整合素，这是胆管上皮细胞的特征。在激素限定培养基中培养的细胞中检测了肝素、DMSO和SB对基因表达的调节作用。AFP、白蛋白、GGT和Yp的调节模式取决于细胞的分化状态。FTO-2B细胞调节基因的方式与E16胎儿肝细胞相似，H4AzC2调节肝细胞和胆管谱系特征性的基因，而H5D.7仅调节胆管基因。一致观察到DMSO对GGT的抑制作用。这三种细胞系表达等量的肝细胞核因子4（HNF-4），但FTO-2B细胞表达更多的肝细胞核因子3β（HNF-3β）和更少的肝细胞核因子3α（HNF-3α），而H4AzC2和H5D.7细胞则相反。
