Metastasis-Associatedmts1Gene Expression Correlates with Increased p53 Detection in the B16 Murine Melanoma

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Abstract
MTS1 is a metastasis-associated gene highly expressed in high-metastasis tumors. Here we show that the expression of the suppressor gene p53 protein correlates with mts1 expression. In murine melanoma B16-F1 cells, α-melanocyte-stimulating hormone up-regulated mts1 and increased p53 positivity in immunohistochemical tests. In B16-ML8 cells, retinoic acid reduced mts1 expression together with a reduction of p53 positivity. The variation of p53 in association with mts1 gene expression suggests that the mts1 product might interact with and stabilize p53. Taxol-induced aneuploidy increased the proportion of G0G1 phase cells, increased p53 positivity, and down-regulated mts1. This suggests that mts1 transcription may have been negatively regulated, possibly on account of the stabilization of microtubules by taxol. We postulate that the control of G1–S transition by p53 could be due to p53 sequestration by mts1, leading to microtubule depolymerization and signaling entry into the S phase. Thus, a coordinated function of mts1 and p53 may be involved not only in uncontrolled growth but also in cytoskeletal depolymerization that could lead to cancer invasion.