Transcriptionally active RNA polymerases from Morris hepatomas and rat liver. Elucidation of the mechanism for the preferential increase in the tumour RNA polymerase I.

Transcriptionally active RNA polymerases from Morris hepatomas and rat liver. Elucidation of the mechanism for the preferential increase in the tumour RNA polymerase I.
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来自 Morris 肝癌和大鼠肝脏的转录活性 RNA 聚合酶。

DOI:
10.1042/bj1900781
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发表时间:
1980
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Jacob,ST
Jacob,ST
中科院分区:
--
文献类型:
--
作者:
Duceman,BW;Jacob,ST

文献摘要

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在从整个组织匀浆中提取酶并随后通过DEAE-Sephadex柱层析进行分级分离后,测定了来自静息肝、再生肝和一系列Morris肝癌(5123 D、7800、7777、3924 A)的DNA依赖性RNA聚合酶I、Ii和III的量和/或活性。当与静息肝脏相比,肿瘤表现出一种特征性的酶模式,其中聚合酶I,而不是II,增加。RNA聚合酶I的增加与肿瘤生长率成正比。聚合酶III的改变仅限于增殖最快的肝癌。相比之下,发现所有类别的RNA聚合酶在肝再生过程中增加。相对于静止的肝脏,生长最快的肿瘤,3924 A,表现出最高的活动和/或量的RNA聚合酶I(8倍)和III(5倍)每克组织。肿瘤RNA聚合酶的这些改变反映在转录活性(结合或染色质相关)酶群体的相应增加中。通过产物分析,阐明了结合型聚合酶I在体外增强肝癌3924 A RNA合成的机制。结果表明,相对于肝脏RNA聚合酶I,肿瘤酶产生更多的新生RNA链,并以更快的速度延长这些链。3 '-末端的数目,如通过掺入尿苷测量的,在肝癌中甚至在防止再起始的条件下也较高。表明肿瘤中转录活性RNA聚合酶I的量增加。
The amount and/or activity of DNA-dependent RNA polymerase I, Ii and III from resting liver, regenerating liver and a series of Morris hepatomas (5123D, 7800, 7777, 3924A) were determined after extraction of the enzymes from whole tissue homogenates and subsequent fractionation by DEAE-Sephadex column chromatography. When compared with resting liver, the tumours exhibited a characteristic enzyme pattern in which polymerase I, but not II, was increased. The increase in RNA polymerase I was proportional to the tumour growth rates. Alterations in polymerase III were confined to the most rapidly proliferating hepatomas. By contrast, all classes of RNA polymerase were found to be increased during liver regeneration. Relative to resting liver, the fastest growing tumour, 3924A, exhibited the highest activities and/or amounts of RNA polymerase I (8-fold) and III (5-fold) per g of tissue. These alterations in the tumour RNA polymerases were reflected in corresponding increases in the transcriptionally active (bound or chromatin-associated) enzyme population. The mechanisms underlying the augmented synthesis of RNA in vitro by bound polymerase I from hepatoma 3924A were elucidated by product analysis. The results indicated that, relative to liver RNA polymerase I, the tumour enzyme produced more nascent RNA chains and elongated these chains at a faster rate. The number of 3'-termini, as measured by incorporation into uridine, was higher in the hepatoma even under conditions which prevented re-initiation. suggesting increased amount of transcriptionally active RNA polymerase I in the tumour.