Metastasis-associated mts1 gene expression correlates with increased p53 detection in the B16 murine melanoma.
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, alpha-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.
Parker
C
C
Cancer Research Unit, University of Newcastle upon Tyne, Medical School, UK.
Lakshmi
M S
MS
Piura
B
B
Sherbet
G V
GV
D002135:Calcium-Binding Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008545:Melanoma / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D009418:S100 Proteins; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D002135:Calcium-Binding Proteins; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D014212:Tretinoin; D009074:Melanocyte-Stimulating Hormones; D017239:Paclitaxel