A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic beta-cells
A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic beta-cells
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ISL-1 在 DLBCL 中呈正反馈调节，但在胰腺 β 细胞中则不然
DOI：
10.1016/j.bbrc.2014.05.021
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发表时间：
2014
影响因子：
3.1
通讯作者：
Zhou Chunyan
中科院分区：
文献类型：
--
作者：
Zhang Qiao;Yang Zhe;Wang Weiping;Guo Ting;Jia Zhuqing;Ma Kangtao;Zhou Chunyan
胰岛素增强子结合蛋白-1（insulin enhancer binding protein-1，ISL-1）是一种具有LIM同源结构域的转录因子，在促进成人胰岛β细胞增殖中发挥重要作用。最近的研究表明ISL-1还可能参与多种肿瘤的发生。然而，ISL-1是否在肿瘤发生中具有任何功能性作用，以及ISL-1在不同条件下的功能差异是完全未知的。在这项研究中，我们发现ISL-1在人胰腺β细胞和弥漫性大B细胞淋巴瘤（DLBCL）中高度表达，但在其他正常组织或肿瘤标本中表达程度要低得多。进一步研究发现，ISL-1可促进胰腺β细胞和DLBCL细胞的增殖，并促进DLBCLin体内成瘤。我们还发现ISL-1不仅可以激活胰腺β细胞中的c-Myc转录，而且可以激活DLBCL细胞中的c-Myc转录。然而，仅在DLBCL细胞中检测到细胞特异性反馈调节。该自调控环是通过ISL-1和c-Myc相互作用形成ISL-1/c-Myc转录复合物，并通过结合ISL-1启动子协同促进ISL-1转录而建立的。综上所述，我们的研究结果表明ISL-1在DLBCL中具有正反馈调节作用，而在胰腺β细胞中没有，这可能导致ISL-1在不同的生理和病理过程中的功能失调。
Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCLin vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.