title: Upregulation of PAX2 promotes the metastasis of esophageal cancer through interleukin-5.
abstract: OBJECTIVE
  This study investigated the clinical relevance and biological function of paired box gene 2 (PAX2) in esophageal squamous cell carcinoma (ESCC).
  
  
  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.
  
  
  CONCLUSIONS
  These findings demonstrate that PAX2 is overexpressed in esophageal carcinoma and IL-5 is identified as PAX2's effector for metastasis.
authors.affiliation: Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Huan
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.forename: Yiting
authors.initials: Y
authors.lastname: Tang
authors.forename: Wenhao
authors.initials: W
authors.lastname: Shen
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Weidong
authors.initials: W
authors.lastname: Shen
authors.forename: Shitao
authors.initials: S
authors.lastname: Zou
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051762:PAX2 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C508599:IL5 protein, human; D015848:Interleukin-5; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human