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双特异性磷酸酶5假基因1(DUSP5P1)在肿瘤细胞中的表达。

Expression of dual-specificity phosphatase 5 pseudogene 1 (DUSP5P1) in tumor cells.

作者信息

Staege Martin S, Müller Katja, Kewitz Stefanie, Volkmer Ines, Mauz-Körholz Christine, Bernig Toralf, Körholz Dieter

机构信息

Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, Germany.

出版信息

PLoS One. 2014 Feb 24;9(2):e89577. doi: 10.1371/journal.pone.0089577. eCollection 2014.

Abstract

Sequencing of individual clones from a newly established cDNA library from the chemoresistant Hodgkin's lymphoma cell line L-1236 led to the isolation of a cDNA clone corresponding to a short sequence from chromosome 1. Reverse transcriptase-polymerase chain reaction indicated high expression of this sequence in Hodgkin's lymphoma derived cell lines but not in normal blood cells. Further characterization of this sequence and the surrounding genomic DNA revealed that this sequence is part of a human endogenous retrovirus locus. The sequence of this endogenous retrovirus is interrupted by a pseudogene of the dual specificity phosphatase 5 (DUSP5). Reverse transcriptase-polymerase chain reaction revealed high expression of this pseudogene (DUSP5P1) in HL cell lines but not in normal blood cells or Epstein-Barr virus-immortalized B cells. Cells from other tumor types (Burkitt's lymphoma, leukemia, neuroblastoma, Ewing sarcoma) also showed a higher DUSP5P1/DUSP5 ratio than normal cells. Furthermore, we observed that higher expression of DUSP5 in relation to DUSP5P1 correlated with the expression of the pro-apoptotic factor B cell leukemia/lymphoma 2-like 11 (BCL2L11) in peripheral blood cells and HL cells. Knock-down of DUSP5 in HL cells resulted in down-regulation of BCL2L11. Thus, the DUSP5/DUSP5P1 system could be responsible for regulation of BCL2L11 leading to inhibition of apoptosis in these tumor cells.

摘要

对来自化疗耐药的霍奇金淋巴瘤细胞系L-1236新建立的cDNA文库中的单个克隆进行测序,导致分离出一个与1号染色体短序列相对应的cDNA克隆。逆转录聚合酶链反应表明该序列在霍奇金淋巴瘤来源的细胞系中高表达,但在正常血细胞中不表达。对该序列及其周围基因组DNA的进一步表征显示,该序列是人类内源性逆转录病毒基因座的一部分。这种内源性逆转录病毒的序列被双特异性磷酸酶5(DUSP5)的假基因中断。逆转录聚合酶链反应显示该假基因(DUSP5P1)在HL细胞系中高表达,但在正常血细胞或爱泼斯坦-巴尔病毒永生化B细胞中不表达。来自其他肿瘤类型(伯基特淋巴瘤、白血病、神经母细胞瘤、尤因肉瘤)的细胞也显示出比正常细胞更高的DUSP5P1/DUSP5比率。此外,我们观察到与DUSP5P1相关的DUSP5的高表达与外周血细胞和HL细胞中促凋亡因子B细胞白血病/淋巴瘤2样11(BCL2L11)的表达相关。HL细胞中DUSP5的敲低导致BCL2L11的下调。因此,DUSP5/DUSP5P1系统可能负责调节BCL2L11,从而导致这些肿瘤细胞凋亡的抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2045/3949351/adfd5e23c9fa/pone.0089577.g001.jpg

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