Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines

BMC Cancer. 2011 Feb 1:11:51. doi: 10.1186/1471-2407-11-51.


Background: CD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers. Our work evaluates the mechanism involved in confluence-dependent CD26 expression in colon cancer.

Methods: Colon adenocarcinoma cells were grown to confluence, and expression of CD26 and transcription factors implicated in its regulation was confirmed by immunofluorescence and Western blotting. Real-time PCR was also performed to evaluate CD26 upregulation at the transcriptional level. The influence of c-Myc on CD26 expression during different growth conditions was further evaluated following transient transfection of a c-Myc-expressing plasmid and a c-Myc specific siRNA.

Results: We found that the colon cancer cell lines HCT-116 and HCT-15 exhibited a confluence-dependent increase in CD26 mRNA and protein, associated with decreased expression of c-Myc, increased USF-1 and Cdx 2 levels, and unchanged HNF-1α expression. Meanwhile, ectopic expression of c-Myc in both cell lines led to decreased CD26 expression. In contrast, transfection of a siRNA targeted to Cdx2 resulted in decreased CD26 level. Importantly, culturing of cells in serum-depleted media, but not acidic conditions, upregulated CD26. While HIF-1α level also increased when cells were cultured in serum-depleted media, its expression was required but not sufficient for CD26 upregulation.

Conclusions: CD26 mRNA and protein levels increase in a confluence-dependent manner in colon carcinoma cell lines, with c-Myc acting as a repressor and Cdx2 acting as an enhancer of CD26 expression. The enhanced expression of CD26 in serum-depleted media and a requirement for HIF-1α suggest a role for nutrients or growth factors in the regulation of CD26 protein expression.

MeSH terms

  • Blotting, Western
  • CDX2 Transcription Factor
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dipeptidyl Peptidase 4 / genetics*
  • Dipeptidyl Peptidase 4 / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • HCT116 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Microscopy, Fluorescence
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transfection


  • CDX2 Transcription Factor
  • Homeodomain Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4