Expression and functional role of Cdx2 in intestinal metaplasia of cystitis glandularis

J Urol. 2013 Sep;190(3):1083-9. doi: 10.1016/j.juro.2013.03.109. Epub 2013 Mar 29.


Purpose: Cdx2 is an essential transcription factor in intestinal epithelial cell differentiation and proliferation. However, to our knowledge the expression and role of Cdx2 in the development of intestinal cystitis glandularis, a metaplastic lesion induced by chronic inflammation, remained to be explored.

Materials and methods: Real-time polymerase chain reaction was used to examine Cdx2, LI-cadherin and villin expression in typical and intestinal cystitis glandularis, and normal bladder tissue. Cdx2 cDNA was subcloned to the retroviral vector pLNCX2 for subsequent transfection into human bladder urothelium cells and rat bladder urothelium. Cdx2 mRNA and protein levels, and cell morphology and proliferation were assessed after transfection using real-time polymerase chain reaction, phase contrast microscopy, transmission electron microscopy and MTT assay, respectively.

Results: Higher mRNA levels of Cdx2, villin and LI-cadherin were detected in intestinal cystitis glandularis compared to normal bladder and typical cystitis glandularis. Only Cdx2 groups attained statistical significance (p <0.001). Retroviral over expression of Cdx2 resulted in increased mRNA and protein expression of Cdx2 as well as villin and LI-cadherin levels, and increased cell proliferation. A distinct change in cellular morphology, in which cells resembled intestinal-like cells, was also observed in vitro and in vivo.

Conclusions: Cdx2 may have a critical role in regulating intestinal metaplasia in cystitis glandularis. Further studies are planned to assess the potential of using Cdx2 as a marker and therapeutic target for cystitis glandularis.

Keywords: BUC; CDH17 protein, human; CDX2 protein, human; CG; Cdx2; Ct; DMEM; Dulbecco's modified Eagle's medium; GAPDH; LI-cadherin; PBS; PCR; bladder urothelium cell; caudal-related homeobox 2; cystitis; cystitis glandularis; glyceraldehyde-3-phosphate dehydrogenase; liver-intestinal cadherin; phosphate buffered saline; polymerase chain reaction; threshold count; urinary bladder; villin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blotting, Western
  • CDX2 Transcription Factor
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Cystitis, Interstitial / genetics*
  • Cystitis, Interstitial / pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics*
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / pathology
  • Metaplasia / genetics
  • Metaplasia / pathology
  • Microscopy, Electron
  • Middle Aged
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Urinary Bladder / pathology*


  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Homeodomain Proteins
  • RNA, Messenger