Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
复制标题
DOI：
10.1186/1471-2164-13-418
复制
发表时间：
2012-08-23
期刊：
影响因子：
4.4
通讯作者：
Heisterkamp N
中科院分区：
文献类型：
--
作者：
Arutyunyan A;Stoddart S;Yi SJ;Fei F;Lim M;Groffen P;Feldhahn N;Groffen J;Heisterkamp N
急性淋巴细胞性白血病（ALL）细胞经药物处理后，如果与保护性基质小鼠胚胎成纤维细胞（MEFs）共培养，则可产生耐药性。我们对这些基质成纤维细胞进行了转录谱分析，以研究它们是否受到药物处理的ALL细胞的影响。这些有丝分裂失活的MEFs基因表达的变化很少，但一个家庭的转录显着增加的序列被确定。我们选择了一个与这个家族相关的序列，将其命名为cassini，用于进一步的鉴定。我们发现cassini在药物处理的ALL细胞中高度上调。对来自不同正常小鼠组织的RNA的分析表明，cassini表达在脾和胸腺中最高，并且可以通过小鼠暴露于细菌内毒素而在这些器官中进一步增强。热休克，而不是其他类型的压力，显着诱导该位点的转录在ALL细胞。卡西尼在人293胚胎肾细胞中的短暂过表达不会增加化疗药物的细胞毒性或细胞抑制作用，但提供了一些保护作用。数据库检索显示，与cassini高度同源的序列存在于啮齿类、顶复门、扁形虫和灵长类动物中，表明它们在进化中是保守的。此外，在长春新碱处理的人ALL细胞中诱导了CASSINI RNA。令人惊讶的是，cassini属于先前报道的小鼠γ-卫星/主要卫星DNA序列家族，这些序列在其他物种中不存在。我们的研究结果表明，这些序列中至少有一个成员的转录受到调节，这表明这在正常和转化的免疫细胞中具有功能。这些序列的表达可以在细胞暴露于特定的应激刺激时保护细胞。
Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs). We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species. Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.
登录
查看更多内容
影响因子：
10.5
作者：
Murre, Cornelis
通讯作者：
Murre, Cornelis
影响因子：
11.4
作者：
Vassen, Lothar;Fiolka, Katharina;Moeroey, Tarik
通讯作者：
Moeroey, Tarik
影响因子：
7
作者：
Kim, Jung-Hyun;Ebersole, Thomas;Larionov, Vladimir
通讯作者：
Larionov, Vladimir
影响因子：
14.9
作者：
HORZ, W;ALTENBURGER, W
通讯作者：
ALTENBURGER, W
影响因子：
5.7
作者：
Fei F;Stoddart S;Groffen J;Heisterkamp N
通讯作者：
Heisterkamp N