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小鼠浆细胞瘤中转位c-myc癌基因的转录激活:肿瘤细胞与增殖正常细胞中RNA水平相似

Transcriptional activation of the translocated c-myc oncogene in mouse plasmacytomas: similar RNA levels in tumor and proliferating normal cells.

作者信息

Keath E J, Kelekar A, Cole M D

出版信息

Cell. 1984 Jun;37(2):521-8. doi: 10.1016/0092-8674(84)90382-9.

Abstract

We examine the influence of the immunoglobulin locus on the expression of the translocated c-myc oncogene in mouse plasmacytomas. The level of c-myc RNA was 30- 35-fold greater in tumor cells than in normal, quiescent B cells. Mitogen stimulation of the lymphocytes with lipopolysaccharide induced a 15-fold increase in c-myc expression per cell to a level that was similar to that in the transcription of the translocated c-myc gene involved initiation from sequences in the first c-myc intron. Abundant RNA transcripts were also found from the noncoding strand of the c-myc intron in most tumor lines. S1 nuclease mapping was used to locate the intronic sequences that are used to initiate the tumor-specific c-myc RNAs. Six different initiation sites within the intron were mapped, none of which have the TATA sequence usually associated with eucaryotic RNA polymerase II promoters. The noncoding strand transcripts were also found to initiate in the c-myc intron. Transcription of the c-myc coding strand was independent of the position of the translocation breakpoint, even when the heavy chain switch and constant regions were deleted.

摘要

我们研究了免疫球蛋白基因座对小鼠浆细胞瘤中易位的c-myc癌基因表达的影响。肿瘤细胞中c-myc RNA的水平比正常静止B细胞中的高30至35倍。用脂多糖对淋巴细胞进行丝裂原刺激可使每个细胞中的c-myc表达增加15倍,达到与涉及从第一个c-myc内含子中的序列起始转录的易位c-myc基因转录水平相似的水平。在大多数肿瘤细胞系中,还从c-myc内含子的非编码链发现了丰富的RNA转录本。用S1核酸酶图谱定位用于起始肿瘤特异性c-myc RNA的内含子序列。在内含子中绘制了六个不同的起始位点,其中没有一个具有通常与真核RNA聚合酶II启动子相关的TATA序列。还发现非编码链转录本也在c-myc内含子中起始。c-myc编码链的转录与易位断点的位置无关,即使重链转换区和恒定区被删除也是如此。

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