Insulin-like growth factor II regulation of gene expression in rat and human hepatomas.
Insulin-like growth factor II regulation of gene expression in rat and human hepatomas.
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胰岛素样生长因子 II 对大鼠和人肝癌基因表达的调节。
DOI：
10.1002/jcp.1041620106
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发表时间：
1995
影响因子：
5.6
通讯作者：
Reid,LM
中科院分区：
文献类型：
--
作者：
Zvibel,I;Brill,S;Reid,LM
胰岛素样生长因子II （IGF II）在肝癌细胞系中调节组织特异性基因的表达，但在原代培养的E14和红细胞缺失的新生大鼠肝细胞中对组织特异性基因的表达没有影响。在这些原代培养中，未观察到α‐胎蛋白（α‐FP）、白蛋白、细胞角蛋白19 （CK 19）、γ‐谷氨酰转肽酶（GGT）和IGF II受体的变化。两种高分化肝癌HepG2和FTO - 2B，以及一种低分化肝癌H4AzC2，在IGF II的存在下没有表现出增殖增加，但在IGF II的作用下表现出基因表达的变化。在HepG2细胞中，IGF II增加了白蛋白mRNA水平，并导致从阳性细胞簇到100%表达免疫组织化学可检测白蛋白的细胞簇的转变。IGF II存在时，胆管标志物CK19和GGT的转录因子HNF‐3β mRNA和蛋白水平也升高。其他测试的基因不受影响，包括α 1‐抗胰蛋白酶和两种肝脏特异性转录因子，HNF‐4和HNF‐3α。在FTO‐2B细胞中，IGF II增加了白蛋白、CK19和GGT的表达，但没有伴随白蛋白和GGT mrna的变化。在h4azc2细胞中，IGF II降低了CK19和OC.3蛋白水平以及GGT、转铁蛋白和HNF‐3β mrna。IGF II对h4azc2细胞的作用在抗大鼠IGF II受体抗体的存在下不被阻断。我们得出结论，IGF II影响肝癌组织特异性基因表达，其对肝癌的定性和定量影响取决于其分化程度。©1995 Wiley‐Liss, Inc。
Insulin‐like growth factor II (IGF II) regulated tissue‐specific gene expression in hepatoma cell lines, but had no effect on expression of tissue‐specific genes in primary cultures of E14 and newborn rat liver cells depleted of erythroid cells. No change was observed in these primary cultures with respect to α‐fetoprotein (α‐FP), albumin, cytokeratin 19 (CK 19), γ‐glutamyltranspeptidase (GGT), and IGF II receptors. Two well‐differentiated hepatomas, HepG2 and FTO‐2B, and a poorly differentiated hepatoma, H4AzC2, did not show increased proliferation in the presence of IGF II, yet showed gene expression changes in response to IGF II. In HepG2 cells, IGF II increased albumin mRNA levels and resulted in a shift from clusters of cells positive to 100% of the cells expressing immunohistochemically detectable albumin. The transcription factor HNF‐3β mRNA and protein levels of the bile duct markers, CK19 and GGT, were also increased in the presence of IGF II. Other genes tested were not affected, including α 1‐antitrypsin, and two liver specific transcription factors, HNF‐4 and HNF‐3α. In FTO‐2B cells, IGF II increased the expression of albumin, CK19, and GGT, without accompanying changes in albumin and GGT mRNAs. In H4AzC2cells, IGF II reduced CK19 and OC.3 protein levels and GGT, transferrin, and HNF‐3β mRNAs. The effects of IGF II on H4AzC2cells were not blocked in the presence of an anti‐rat IGF II receptor antibody. We conclude that IGF II affects tissue‐specific gene expression of hepatomas and qualitative and quantitative aspects of its influence on the hepatomas is dependent on their degree of differentiation. © 1995 Wiley‐Liss, Inc.