Coexpression and nuclear colocalization of metastasis-promoting protein S100A4 and p53 without mutual regulation in colorectal carcinoma |
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Authors: | Gisle Berge Daniela Elena Costea Marianne Berg Heidi Rasmussen Ida Grotterød Ragnhild A Lothe Gunhild M Mælandsmo Kjersti Flatmark |
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Institution: | (1) Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0310 Oslo, Norway;(2) Section of Pathology, The Gade Institute, University of Bergen, 5021 Bergen, Norway;(3) Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0310 Oslo, Norway;(4) Centre for Cancer Biomedicine, University of Oslo, 0310 Oslo, Norway; |
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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. |
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