Upregulation of PAX2 Promotes the Metastasis of Esophageal Cancer through Interleukin-5
Upregulation of PAX2 Promotes the Metastasis of Esophageal Cancer through Interleukin-5
复制标题
PAX2上调通过IL-5促进食管癌转移
DOI：
10.1159/000369734
复制
发表时间：
2015-01-01
影响因子：
--
通讯作者：
Zhang, Shuyu
中科院分区：
文献类型：
--
作者：
Liu, Pengfei;Gao, Yi;Zhang, Shuyu
背景/目标：本研究旨在探讨配对盒基因2（PAX 2）在食管鳞状细胞癌（ESCC）中的临床意义和生物学功能。方法/结果：结果显示PAX 2在120例食管鳞癌组织中的表达明显增高，其表达与食管鳞癌分期（P = 0.001）、淋巴结转移（P = 0.019）和淋巴管浸润（P = 0.005）有关。此外，PAX 2过表达导致ESCC TE-1和Eca-109细胞的细胞增殖显著降低，但转移能力增加。用短发夹RNA敲低PAX 2表达证实了在ESCC细胞中促进转移的作用。mRNA微阵列筛选显示PAX 2过表达影响在多个通路中发挥功能的多个基因。进一步更详细地研究了由PAX 2诱导的并且已显示促进肿瘤转移的白细胞介素-5（IL-5）。在IL-5启动子中鉴定了两个PAX 2结合位点，并且观察到PAX 2刺激食管癌细胞中的IL-5启动子活性和IL-5表达。染色质免疫沉淀（ChIP）证实PAX 2在IL-5启动子中的直接结合。PAX 2 mRNA和IL-5 mRNA在正常食管和食管鳞癌组织中的表达呈显著正相关。结论：PAX 2在食管癌组织中高表达，IL-5可能是PAX 2促进食管癌转移的效应因子。
Background/Aims: This study investigated the clinical relevance and biological function of paired box gene 2 (PAX2) in esophageal squamous cell carcinoma (ESCC). Methods/Results: Results showed that PAX2 expression was significantly increased in tumor tissues and that its expression correlated with the ESCC stage (P = 0.001), lymph node metastasis (pN, P = 0.019) and lymphatic invasion (P = 0.005) in 120 ESCC tissue specimens by immunohistochemistry. Furthermore, PAX2 overexpression resulted in markedly reduced cell proliferation but increased metastasis capacity in ESCC TE-1 and Eca-109 cells. Knockdown of PAX2 expression with a short hairpin RNA confirmed a role in the promotion of metastasis in ESCC cells. mRNA microarray screening revealed that PAX2 overexpression affected multiple genes that function in multiple pathways. Interleukin-5 (IL-5), which was induced by PAX2 and has been shown to promote tumor metastasis, was further studied in greater detail. Two PAX2 binding sites were identified in the IL-5 promoter, and PAX2 was observed to stimulate IL-5 promoter activity and IL-5 expression in esophageal cancer cells. Chromatin immunoprecipitation (ChIP) confirmed the direct binding of PAX2 in the IL-5 promoter. The expression of PAX2 mRNA significantly correlated with that of IL-5 in normal esophageal and ESCC tissues. Conclusion: These findings demonstrate that PAX2 is overexpressed in esophageal carcinoma and IL-5 is identified as PAX2's effector for metastasis.