Enterocyte-like differentiation of the Caco-2 intestinal cell line is associated with increases in AP-1 protein binding

Qingming Ding, Zizheng Dong, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The nuclear factor AP-1, a large family of transcription factors composed of the Jun and Fos protein families, plays a role in the differentiation of various cells; the role of the AP, 1 factors in intestinal differentiation is not known. Members of the AP-1 family can be activated by the Ras pathway and, in addition, Ras appears to be important for gut differentiation. The purpose of this study was to determine whether AP-1 activity is altered in the Caco-2 cell lines which spontaneously differentiates to a small bowel phenotype after confluency, and the Caco-2- ras cell line, which exhibits differentiated properties regardless of culture conditions. AP-1 binding activity, consisting of c-Jun, JunD, c-Fos and Fra- 2 proteins, was increased in Caco-2 cells at 3 days postconfluency, a time point associated with G1 block and cessation of proliferation. Steady state levels of JunD were increased at day 3 postconfluency as determined by Western blot. Furthermore, AP-1 binding was increased in preconfluent Caco- 2-ras cells compared with parental Caco-2 cells, suggesting that AP-1 induction may be mediated by the Ras pathway. The early induction of AP-1 binding activity suggests a role for these proteins in the differentiation of the Caco-2 intestinal cell line.

Original languageEnglish
Pages (from-to)175-182
Number of pages8
JournalLife Sciences
Issue number3
StatePublished - Dec 11 1998

Bibliographical note

Funding Information:
The authorsw ish to thank Eileen Figueroa and Karen Martin for manuscriptp reparation. This work was supportedb y grants ROl DK48498, ROl AG10885 and PO1 DK35608 from the National Instituteso f Health.


  • AP-1 factors
  • Caco-2 cell line
  • Intestinal differentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Pharmacology, Toxicology and Pharmaceutics (all)


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