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胎儿肝细胞与肝癌细胞杂交体中正常和肿瘤性甲胎蛋白基因的差异调控

Differential regulation of normal and tumor alpha 1-fetoprotein genes in fetal hepatocyte x hepatoma hybrids.

作者信息

Gingras M C, Szpirer J, Turcotte B, Bélanger L, Szpirer C

机构信息

Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Canada.

出版信息

Cancer Res. 1988 Nov 15;48(22):6371-4.

PMID:2460223
Abstract

Fetal rat hepatocytes and mouse hepatoma cells actively expressing alpha 1-fetoprotein (AFP) and albumin genes were fused with the use of Sendai virus, and the expression of normal (rat) and tumor (mouse) AFP and albumin genes was analyzed in hybrid clones. The tumor AFP gene and both albumin genes were active in 103 hybrids. Expression of the normal fetal rat AFP gene, however, was maintained in only 3 hybrids, and it was frequently lost or decreased selectively upon subcloning. Furthermore, the normal AFP gene, when expressed, was more reactive than the tumor AFP gene to repression by a glucocorticosteroid hormone. These results suggest constitutive differences in the manner an oncofetal gene is activated and regulated in normal and neoplastic states. AFP gene expression in normal hepatocytes appears to be subordinated to a differentiation program degenerated and bypassed in hepatoma cells.

摘要

利用仙台病毒将活跃表达α1-甲胎蛋白(AFP)和白蛋白基因的胎鼠肝细胞与小鼠肝癌细胞融合,并在杂交克隆中分析正常(大鼠)和肿瘤(小鼠)AFP及白蛋白基因的表达情况。肿瘤AFP基因和两个白蛋白基因在103个杂交细胞中均有活性。然而,正常胎鼠AFP基因仅在3个杂交细胞中得以维持表达,并且在亚克隆时经常选择性地丢失或表达降低。此外,正常AFP基因一旦表达,相较于肿瘤AFP基因,对糖皮质激素的抑制作用反应更为敏感。这些结果表明,癌胚基因在正常和肿瘤状态下的激活和调控方式存在组成性差异。正常肝细胞中的AFP基因表达似乎从属于一个在肝癌细胞中退化且被绕过的分化程序。

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Differential regulation of normal and tumor alpha 1-fetoprotein genes in fetal hepatocyte x hepatoma hybrids.胎儿肝细胞与肝癌细胞杂交体中正常和肿瘤性甲胎蛋白基因的差异调控
Cancer Res. 1988 Nov 15;48(22):6371-4.
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Phenotypic characterization of rat hepatoma cell lines and lineage-specific regulation of gene expression by differentiation agents.大鼠肝癌细胞系的表型特征及分化剂对基因表达的谱系特异性调控
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Expression of an oncodevelopmental gene product (alpha-fetoprotein) during fetal development and adult oncogenesis.一种肿瘤发生发展相关基因产物(甲胎蛋白)在胎儿发育和成人肿瘤发生过程中的表达。
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In situ hybridization studies on expression of albumin and alpha-fetoprotein during the early stage of neoplastic transformation in rat liver.大鼠肝脏肿瘤转化早期白蛋白和甲胎蛋白表达的原位杂交研究
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