Objective      To investigate the roles of Krüppel-like factor 4 (KLF4) and caudal-related homeodomain transcription factor 2 (CDX2) in the development of Barrett’s esophagus (BE) induced by deoxycholic acid (DCA).       Methods      Immunohistochemical SP staining was applied to evaluate the expression levels of KLF4 nd CDX2 in 49 samples of normal esophageal tissues and 22 samples of BE tissues. Human esophagus epithelial cell line Het-1A was treated with DCA for 0

4

8 and 12 h. The siRNA of KLF4 was designed and transfected into Het-lA cells. The Het-lA cells were assigned into blank group

negative control-siRNA group

negative control-siRNA+DCA treatment group

KLF4-siRNA group

and KLF4-siRNA+DCA treatment group. The Het-1A cells with KLF4 over-expression were also established by transfection of over-expression recombinant lentivirus into the cells. Then

the expression levels of KLF4

CDX2 and MUC2 at mRNA and protein levels were detected by real-time PCR and Western blot assay

respectively.       Results       Among the 22 patients with BE

immunohistochemical staining indicated that 15 cases had positive expression of KLF4 (68.18%)

which mainly located in the nucleus

and 16 cases had positive expression of CDX2 (72.73%)

mainly located in the nucleus too. KLF4 and CDX2 was strongly expressed in the BE tissues

and its level was significantly higher in the BE compared with normal esophageal tissues (Chi square=18.642

P0.05; Chi square=23.678

P0.05). Real-time PCR and Western blot assay revealed that the mRNA and protein levels of KLF4

CDX2 and MUC2 were enhanced in a time-dependent manner in Het-lA cells induced by DCA (P0.05)

their levels were significantly suppressed in KLF4-siRNA groups

and could not be enhanced by stimulation of DCA again

but the levels were significantly increased in KLF4-overexpression group.       Conclusion      DCA up-regulates the expression of CDX2 by KLF4

which cause higher expression of MUC2 and thus promote the transformation of normal esophageal epithelia to BE.