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Nuclear location of the metastasis associated protein S100A4 was previously shown to correlate with disease stage at diagnosis in a panel of 316 colorectal tumor samples, but the nuclear function of S100A4 is still unclear. A number of potential interacting protein partners located in the nucleus have been suggested, among them p53. Experimental data have led to the hypothesis that S100A4 presence will contribute to apoptotic cell death in cells harboring wt p53, thus suggesting a potential mechanism for selection of a metastatic phenotype. If this were the case, the presence of S100A4 and wt p53 should be mutually exclusive, and the present study was undertaken to assess whether this mechanism would be relevant in colorectal cancer (CRC).

Forty CRC tumor samples were selected based on the presence or absence of detectable S100A4 by immunohistochemistry, and p53 mutational status was determined. Similarly, a panel of CRC cell lines with known p53 mutational status was analyzed for S100A4 levels, and additionally, S100A4 and p53 were experimentally up- or down regulated in in vitro model systems to assess reciprocal effects.

No correlation was found between the presence of nuclear or cytoplasmic S100A4 and p53 mutational status in human tumors or cell lines. Furthermore, over expression or down regulation of S100A4 did not influence p53 expression levels in in vitro experimental systems. Similarly, over expression of p53 did not affect S100A4 levels. In conclusion, the presence of S100A4 was independent of p53 mutational status in CRC tumor samples and cell lines and no reciprocal regulation was observed in vitro.

Irrespective of p53 status, a direct or indirect interaction between S100A4 and p53 could affect downstream p53 target genes.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA