Journal of Cancer Research and Clinical Oncology

, Volume 129, Issue 12, pp 703–708

EphA2 Up-regulation induced by deoxycholic acid in human colon carcinoma cells, an involvement of extracellular signal-regulated kinase and p53-independence

  • Zhongyou Li
  • Masamitsu Tanaka
  • Hideki Kataoka
  • Ritsuko Nakamura
  • Ravshanov Sanjar
  • Kazuya Shinmura
  • Haruhiko Sugimura
Original Paper

Abstract

Purpose

The EphA2 receptor protein tyrosine kinase gene has been shown to be over-expressed or functionally altered in a number of human tumors, including colon cancer, but little is known about the regulation of this new oncoprotein. In order to explore the mechanism of EphA2 up-regulation in cancer cells, we examined the change of expression of EphA2 gene induced by deoxycholic acid (DCA) and elucidated its possible pathways in human colon cancer cells.

Methods

Western blot and RT-PCR were used to assess the protein expression and messenger RNA in several colon cancer cell lines, which harbor various p53 status. The inhibition study to interfere the MAPK pathway was performed by using various chemicals and by transfecting dominant negative mutant plasmids.

Results

Up-regulation of EphA2 induced by DCA was observed in a dose- and time-dependent fashion both in mRNA and protein levels. This regulation is constant regardless of p53 status including wild, mutant or knocked out in the colon cell lines used. This induction was in part blocked by either erk1/2 inhibitors or dominant negative mutants erk1/2 plasmids.

Conclusions

These results suggest that DCA induced up-regulation of EphA2 in colon cancer cells is due to activation of erk1/2 cascade, and is p53-independent. Taken together with the roles of EphA2 and DCA in tumorigenesis, which have been independently reported, our observation will provide a new mechanistic basis of DCA commitment in carcinogenesis.

Keywords

Colon cancer EphA2 Deoxycholic acid Extracellular signal-regulated kinase p53 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Zhongyou Li
    • 1
  • Masamitsu Tanaka
    • 1
  • Hideki Kataoka
    • 1
  • Ritsuko Nakamura
    • 1
  • Ravshanov Sanjar
    • 1
  • Kazuya Shinmura
    • 1
  • Haruhiko Sugimura
    • 1
  1. 1.The First Department of PathologyHamamatsu University School of MedicineHamamatsuJapan

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