Invasion of v-Fos(FBR)-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes.

Autor: McGarry LC; Beatson Laboratories, Beatson Institute for Cancer Research, Cancer Research UK, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Winnie JN, Ozanne BW
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2004 Jul 08; Vol. 23 (31), pp. 5284-92.
DOI: 10.1038/sj.onc.1207687
Abstrakt: Transformation of fibroblasts with the v-fos oncogene produces a highly invasive phenotype that is mediated by changes in gene expression. Inhibition of histone deacetylase (HDAC) activity with trichostatin A (TSA) or valproic acid (VPA) at concentrations that do not affect morphology, motility, chemotaxis or proliferation, strongly inhibits invasion and results in the re-expression of a significant proportion of those genes that are downregulated in the v-Fos-transformed cells. Independent expression of three of these re-expressed genes, (Ring1 and YY1 binding protein (RYBP); protocadherin gamma subfamily C,3 (PCDHGC3); and signal transducer and activator of transcription 6 (STAT6)) in Fos-transformed cells, has no effect on morphology, motility, chemotaxis or proliferation, but strongly inhibits invasion. Therefore, we conclude that the ability of v-Fos-transformed cells to invade is dependent upon repression of gene expression through either direct or indirect HDAC activity.
Databáze: MEDLINE