Translocated c-myc oncogene of Burkitt lymphoma is transcribed in plasma cells and repressed in lymphoblastoid cells.
Translocated c-myc oncogene of Burkitt lymphoma is transcribed in plasma cells and repressed in lymphoblastoid cells.
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伯基特淋巴瘤的易位 c-myc 癌基因在浆细胞中转录并在类淋巴母细胞中受到抑制。
DOI：
10.1073/pnas.81.10.3170
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发表时间：
1984
影响因子：
11.1
通讯作者：
Nishikura,K
中科院分区：
文献类型：
--
作者：
Croce,CM;Erikson,J;ar-Rushdi,A;Aden,D;Nishikura,K
我们检查了伯基特淋巴瘤细胞与人淋巴母细胞或小鼠浆细胞瘤细胞之间的体细胞杂交体，以检测易位的 c-myc 癌基因的表达。这项研究的结果表明，易位的 c-myc 癌基因在浆细胞中转录，但在类淋巴母细胞中受到抑制。因此，易位c-myc转录所需的因子存在于浆细胞和伯基特淋巴瘤细胞中，但在类淋巴母细胞中不存在或失活。由于重排的免疫球蛋白位点与c-myc癌基因之间的距离甚至可以超过30-50 kilobase，我们推测易位的c-myc癌基因受到能够长距离作用的增强子样元件的转录控制。这种远程增强子的活性可能取决于与在浆细胞和伯基特淋巴瘤细胞中活跃但在类淋巴母细胞中不活跃的反式作用因子的相互作用。我们还检查了 c-myc 癌基因第一个外显子的转录，由于涉及第一个内含子的染色体断裂，该癌基因与第二个和第三个外显子分离。该外显子在带有 t(8;14) 染色体易位的 ST486 Burkitt 淋巴瘤细胞中以高水平转录。类淋巴母细胞和 ST486 细胞之间的杂交细胞表达高水平的第一个外显子转录物，而浆细胞和 ST486 细胞之间的杂交细胞则不然。因此，分离的第一个外显子的转录可以在类淋巴母细胞和伯基特淋巴瘤细胞中增强，因为它与通常位于 C mu 基因的连接区和转换区之间的重链增强子非常接近。然而，这种增强不会发生在浆细胞中，可能是因为这些细胞能够完全抑制 c-myc 癌基因，除非它被放置在重排的免疫球蛋白恒定区基因附近。
We examined somatic cell hybrids between Burkitt lymphoma cells and either human lymphoblastoid cells or mouse plasmacytoma cells for the expression of the translocated c-myc oncogene. The results of this study indicate that the translocated c-myc oncogene is transcribed in plasma cells but is repressed in lymphoblastoid cells. Thus, the factors necessary for translocated c-myc transcription are present in plasma cells and Burkitt lymphoma cells but are absent or inactive in lymphoblastoid cells. Since the distance between the rearranged immunoglobulin loci and the c-myc oncogene can even exceed 30-50 kilobases, we speculate that the translocated c-myc oncogene is under the transcriptional control of enhancer-like elements capable of acting over long distances. The activity of this long-range enhancer may depend on the interaction with transacting factors that are active in plasma cells and in Burkitt lymphoma cells but are not active in lymphoblastoid cells. We also examined the transcription of the first exon of the c-myc oncogene, which becomes separated from the second and third exon because of the chromosomal break involving the first intron. This exon is transcribed at high levels in ST486 Burkitt lymphoma cells with the t(8;14) chromosome translocation. Hybrids between lymphoblastoid and ST486 cells expressed high levels of transcripts of the first exon, whereas hybrids between plasma cells and ST486 cells did not. Thus, transcription of the separated first exon can be enhanced in lymphoblastoid and Burkitt lymphoma cells because of its close proximity to the heavy chain enhancer that is normally located between the joining and the switch region of the C mu gene. Such enhancement, however, does not occur in plasma cells, possibly because these cells are able to suppress completely the c-myc oncogene, unless it has been placed in the proximity of a rearranged immunoglobulin constant region gene.