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

摘要

ABSTRACTMTS1is a metastasis-associated gene highly expressed in high-metastasis tumors. Here we show that the expression of the suppressor genep53protein correlates withmts1expression. In murine melanoma B16-F1 cells, α-melanocyte-stimulating hormone up-regulatedmts1and increased p53 positivity in immunohistochemical tests. In B16-ML8 cells, retinoic acid reducedmts1expression together with a reduction of p53 positivity. The variation of p53 in association withmts1gene expression suggests that themts1product might interact with and stabilize p53. Taxol-induced aneuploidy increased the proportion of G0G1phase cells, increased p53 positivity, and down-regulatedmts1. This suggests thatmts1transcription 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 invasi