Metastasis associated MTS1 and NM23 genes affect tubulin polymerisation in B16 melanomas: a possible mechanism of their regulation of metastatic behaviour of tumours.
The nm23 and mts1 genes are associated with the expression of the metastatic phenotype. We have shown previously that modulation of metastatic behaviour produces parallel changes in the expression of these genes and that the expression of the two genes is co-regulated. Here we show that modulation of gene expression affects the process of tubulin polymerisation. B16 melanoma cell lines F1 and ML8 were treated with alpha melanocyte stimulating hormone (MSH) and all-trans retinoic acid (RA) respectively. MSH reduced the proportion of nm23+ and increased mts1+ F1 cells, with a 55% decrease in the ratio nm23:mts1. In parallel, MSH increased the expression of depolymerised form of tubulin in these cells. Treatment of ML8 cells with RA decreased mts1 positivity to a greater extent that nm23 positivity and the nm23:mts1 ratio increased by 70% and, in parallel, reduced the expression of depolymerised form of tubulin. These data suggest that nm23 and mts1 gene expression regulates the biological behaviour of the tumour cell and confer on it invasive and metastasizing properties by affecting the state of tubulin polymerisation.
Cancer Research Unit, Medical School, University of Newcastle upon Tyne.
M S
MS
Lakshmi
C
C
Parker
G V
GV
Sherbet
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase; D011506:Proteins / Q000235:genetics*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D000521:alpha-MSH / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D014157:Transcription Factors; D014404:Tubulin; D014212:Tretinoin; D000521:alpha-MSH; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins