CCAAT/Enhancer-binding Proteins and Interact with the Silencer Element in the Promoter of Glutathione S-Transferase P Gene during Hepatocarcinogenesis (*)
CCAAT/Enhancer-binding Proteins and Interact with the Silencer Element in the Promoter of Glutathione S-Transferase P Gene during Hepatocarcinogenesis (*)
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肝癌发生过程中 CCAAT/增强子结合蛋白并与谷胱甘肽 S-转移酶 P 基因启动子中的沉默元件相互作用 (*)
DOI：
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发表时间：
1995
影响因子：
4.8
通讯作者：
M. Imagawa
中科院分区：
文献类型：
--
作者：
S. Osada;K. Takano;T. Nishihara;Toshiya Suzuki;M. Muramatsu;M. Imagawa
我们之前已经在谷胱甘肽s -转移酶P （GST-P）基因中发现了一个沉默者，该基因在化学性肝癌发生过程中强烈特异性表达。消声器中至少有三个交互作用因子与多个顺式元件结合。其中，Silencer Factor-B （SF-B）与CCAAT/增强子结合蛋白β (C/EBPβ)相同，并结合GST-P Silencer 1 （GPS1）。许多C/EBPβ结合位点被每个C/EBP异构体识别。化学肝癌发生过程中C/EBP异构体的Western blot分析显示C/EBPα表达降低。然而，C/EBPβ水平没有变化。在正常肝核提取物中，C/EBPα是与GPS1结合的主要形式，而在致癌肝核提取物中，C/EBPα和C/EBPβ都与GPS1结合。此外，转染实验表明，C/EBPα不仅抑制GST-P启动子活性，还能减弱C/EBPβ对GST-P的转录刺激。以上结果表明，C/EBPα与C/EBPβ的比值是GST-P沉默因子活性的重要影响因素之一，在肝癌发生过程中，该比值的降低降低了GST-P沉默因子活性，从而增加了GST-P的表达。
We have previously identified a silencer in the glutathione S-transferase P (GST-P) gene which is strongly and specifically expressed during chemical hepatocarcinogenesis. At least three trans-acting factors bind to multiple cis-elements in the silencer. One of them, Silencer Factor-B (SF-B), is identical with CCAAT/enhancer-binding protein β (C/EBPβ) and binds to GST-P Silencer 1 (GPS1). Many C/EBPβ binding sites are recognized by each of the C/EBP isoforms. Western blot analyses of C/EBP isoforms during chemical hepatocarcinogenesis revealed a decrease of C/EBPα expression. However, there was no change in C/EBPβ level. In the nuclear extracts from normal liver, C/EBPα was the dominant form that bound to GPS1, whereas both C/EBPα and C/EBPβ bound to GPS1 in the nuclear extracts from carcinogenic liver. Furthermore, transfection assays showed that C/EBPα not only repressed the GST-P promoter activity but also attenuated the transcriptional stimulation by C/EBPβ. These observations strongly suggest that the ratio of C/EBPα to C/EBPβ is one of the important factors for the GST-P silencer activity, and the decrease of this ratio during hepatocarcinogenesis reduces the silencer activity and, consequently, increases the GST-P expression.
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DOI：
10.1073/pnas.90.20.9606
发表时间：
1993-10-15
影响因子：
11.1
作者：
LIN, FT;MACDOUGALD, OA;LANE, MD
通讯作者：
LANE, MD
影响因子：
10.5
作者：
S. C. Williams;Carrie A. Cantwell;P. Johnson
通讯作者：
S. C. Williams;Carrie A. Cantwell;P. Johnson
DOI：
10.1073/pnas.89.17.8145
发表时间：
1992-09-01
影响因子：
11.1
作者：
LECLAIR, KP;BLANAR, MA;SHARP, PA
通讯作者：
SHARP, PA
影响因子：
10.5
作者：
CHRISTY, RJ;YANG, VW;LANE, MD
通讯作者：
LANE, MD
DOI：
10.1073/pnas.87.1.251
发表时间：
1990-01-01
影响因子：
11.1
作者：
KAESTNER, KH;CHRISTY, RJ;LANE, MD
通讯作者：
LANE, MD