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Amino Acids

, Volume 41, Issue 4, pp 875–884 | Cite as

Coexpression and nuclear colocalization of metastasis-promoting protein S100A4 and p53 without mutual regulation in colorectal carcinoma

  • Gisle Berge
  • Daniela Elena Costea
  • Marianne Berg
  • Heidi Rasmussen
  • Ida Grotterød
  • Ragnhild A. Lothe
  • Gunhild M. Mælandsmo
  • Kjersti Flatmark
Original Article

Abstract

Nuclear localization of the metastasis-associated protein S100A4 has been shown to correlate with advanced disease stage in primary colorectal carcinomas (CRC), but nuclear function and its relevance for the metastatic capacity of tumor cells is still unclear. Among several nuclear interacting protein partners suggested for S100A4, the tumor suppressor protein p53 has attracted particular interest, and previous studies suggest direct and indirect modes of interaction between the two proteins. The present study was undertaken to assess coexpression and potential interaction in CRC. TP53 mutational status and S100A4 expression were investigated in a selected series of primary CRC specimens (n = 40) and cell lines (n = 17) using DNA sequencing, western blot, and double immunostaining. Additionally, S100A4 and p53 were experimentally up- and down-regulated in vitro to assess reciprocal effects. For the first time, S100A4 and p53 coexpression was demonstrated in individual CRC cells, with nuclear colocalization as a particularly interesting feature. In contrast to previous studies, no correlation was observed between TP53 mutational status and S100A4 expression, and no evidence was obtained to support reciprocal regulation between the two molecules in the HCT116 isogenic cell line model. In conclusion, S100A4 and p53 were shown to be colocalized in individual nuclei of CRC cells, and it might be speculated whether the proteins interact in this subcellular compartment.

Keywords

Colorectal neoplasms S100A4 p53 TP53 Metastasis 

Notes

Acknowledgments

We would like to thank Dr. Bert Vogelstein for kindly making the isogenic HCT116 cell model and p53 constructs available to us, Sigurd Bø for providing the siRNA constructs and Gunnvor Øijordsbakken for excellent technical assistance. The present work was supported by postdoctoral grants to K.F. (Norwegian Research Council, Grant Number 160604/V50), G.B. (Norwegian Cancer Society, Grant Number C99026) and D.E.C (Norwegian Research Council, Grant Number 178601), and by a PhD grant to M.B. (Norwegian Cancer Society, RAL: Grant Number A95068) and project support from the Functional Genomics Program in the Norwegian Research Council (Grant Number 152004/S10).

Conflict of interest statement

The authors declare no conflict of interest.

Supplementary material

726_2010_514_MOESM1_ESM.doc (812 kb)
Supplementary material 1 (DOC 812 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gisle Berge
    • 1
  • Daniela Elena Costea
    • 2
  • Marianne Berg
    • 3
    • 4
  • Heidi Rasmussen
    • 1
  • Ida Grotterød
    • 1
  • Ragnhild A. Lothe
    • 3
    • 4
  • Gunhild M. Mælandsmo
    • 1
  • Kjersti Flatmark
    • 1
  1. 1.Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  2. 2.Section of Pathology, The Gade InstituteUniversity of BergenBergenNorway
  3. 3.Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  4. 4.Centre for Cancer BiomedicineUniversity of OsloOsloNorway

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