A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic beta-cells

作者：Zhang Qiao; Yang Zhe; Wang Weiping; Guo Ting; Jia Zhuqing; Ma Kangtao; Zhou Chunyan^*

来源：Biochemical and Biophysical Research Communications, 2014, 449(3): 295-300.

DOI：10.1016/j.bbrc.2014.05.021

• 1SL-1
• Pancreatic beta-cell
• DLBCL
• Feedback regulation

Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic beta-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 beta-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 beta-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic beta-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 beta-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

• 出版日期2014-7-4
• 单位北京大学