Lee Jae Yong, Park Young Joon, Oh Nuri, Kwack Kyu Bum, Park Kyung-Soon
Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
Oncotarget. 2017 Jun 27;8(26):42752-42760. doi: 10.18632/oncotarget.17459.
Interleukin-20 (IL-20) is a member of the IL-10 family. IL-20 expression is regulated by a transcription elongation factor, Ell3, in estrogen receptor-positive (ER(+)) breast cancer cells. In this study, we demonstrated that ER(α), GATA3 and FOXA1 form a transcriptional complex with Ell3 to regulate IL-20 expression in ER(+) breast cancer cells. We also determined that GATA3 and FOXA1 share a binding site with ER(α) in the interleukin-20 promoter. Furthermore, we found that FOXA1 represses IL-20 expression, whereas GATA3 and ER(α) activate it. In addition, we demonstrated that Ell3 associates with ER(α) to increase its binding affinity to the IL-20 promoter, which may prevent FOXA1 binding to the same region of this promoter. Our results expand upon the current understanding of the regulatory mechanism of IL-20 in cancer.
白细胞介素-20(IL-20)是IL-10家族的一员。在雌激素受体阳性(ER(+))乳腺癌细胞中,IL-20的表达受转录延伸因子Ell3调控。在本研究中,我们证明了ER(α)、GATA3和FOXA1与Ell3形成转录复合物,以调控ER(+)乳腺癌细胞中IL-20的表达。我们还确定,GATA3和FOXA1在白细胞介素-20启动子中与ER(α)共享一个结合位点。此外,我们发现FOXA1抑制IL-20的表达,而GATA3和ER(α)则激活它。另外,我们证明Ell3与ER(α)结合,增加其与白细胞介素-20启动子的结合亲和力,这可能会阻止FOXA1与该启动子的同一区域结合。我们的研究结果拓展了目前对癌症中IL-20调控机制的认识。