Sequential expression of c-oncs in regenerating liver.

再生肝脏中 c-oncs 的顺序表达。

• 批准号: 63570316
• 负责人: KANEKO Yoshiyasu
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570316/
• 关键词: Liver regeneration; oncogene; cell growth factor; mRNA; 細胞癌遺伝子; 転写調節機構; 肝細胞

In regenerating liver, cellular oncogenes such as c-fos and c-myc are expressed sequentially. To analyze the molecular mechanism of gene expression in vitro, we tried to develop cell culture system in which oncogenes were expressed sequentially. Human hepatocytes and hepatoma cells were growth arrested by culturing in serum-free medium and then stimulated with serum. Transient and sequential increases in c-fos and c-myc mRNAs were observed which resembled the in vivo liver regeneration after partial heaptectomy. Using these in vitro culture system, we analyzed the effect of various growth factors and growth inhibitors. Both EGF and PDGF stimulated the sequential expression of c-fos and c-myc gene. Tumor promoter teleocidin and butyrate inhibited the growth of the hepatoma cells and the expression of c-myc. The change of c-myc expression was not associated with the alteration of the higher structure of c-myc gene as measured by DNase I hypersensitivity. On the other hand, novobiocin, a topoisomerase II inhibitor, reduced the DNase I sensitivity of c-myc without reducing c-myc mRNA. These results may suggest that the analysis of transcription factors by gel retardation assay using specific promoter of c-oncs is necessary to provide further information about the expression of c-oncs.

在再生肝脏中，细胞癌基因如c-fos和c-myc依次表达。为了分析体外基因表达的分子机制，我们试图建立癌基因顺序表达的细胞培养系统。人肝细胞和肝癌细胞通过在无血清培养基中培养而生长停滞，然后用血清刺激。观察到c-fos和c-myc mRNA的瞬时和连续增加，这类似于部分肝切除术后的体内肝再生。利用这些体外培养体系，我们分析了各种生长因子和生长抑制剂的作用。EGF和PDGF均能刺激c-fos和c-myc基因的顺序表达。肿瘤促进剂teleocidin和butyrate抑制肝癌细胞的生长和c-myc的表达。c-myc表达的变化与DNase I超敏反应测定的c-myc基因高级结构的改变无关。另一方面，新生霉素，拓扑异构酶II抑制剂，降低c-myc的DNA酶I的敏感性，而不减少c-myc mRNA。这些结果表明，利用c-oncs特异性启动子进行凝胶阻滞分析转录因子对进一步了解c-oncs的表达是必要的。

项目成果

金子義保: 内科. 61. 608-611 (1988)

金子义康：内科医学。61。608-611（1988）

金子義保: "α-フェトプロテイン、inケ-ススタディ検査値の診断プロセス" 中外医学社, 229 (1989)

Yoshiyasu Kaneko：“甲胎蛋白的诊断过程，案例研究测试值”中外医学社，229（1989）

Kaneko Y.: "Liver regeneration and oncogene" Hepatology (eds Hoshi, T., and Iriki, M.) Nannkoudou,.

Kaneko Y.：“肝脏再生和癌基因”肝病学（Hoshi，T. 和 Iriki，M. 编）Nannkoudou，。

金子義保: "αフェトプロティン,inケ-ススタディ検査値の診断プロセス" 中外医学社, 229 (1989)

Yoshiyasu Kaneko：“案例研究测试值中甲胎蛋白的诊断过程”《中外医学社》，229（1989）

金子義保: "肝癌と遺伝子" 内科. 61. 608-611 (1988)

Yoshiyasu Kaneko：“肝癌和基因”内科 61. 608-611 (1988)。