Down-regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells - Archive ouverte HAL Access content directly
Journal Articles International Journal of Cancer Year : 2009

Down-regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells

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Abstract

The RB18A/MED1 human gene, also named TRAP220, DRIP205 and PBP, encodes for a single 205 kDa component, which interacts with nuclear receptors and transcription factors. RB18A/MED1 chromosome localization on locus 17q12-q21.1 suggests its involvement in human cancers. We herein analyzed RB18A/MED1 expression in human melanoma cell lines. We found that RB18A/MED1 is either highly or weakly expressed in melanoma cells, depending on their respectively non or highly-tumorigenic phenotype. We therefore investigated the possible existence of a relationship between the RB18A/MED1 expression level and melanoma cell phenotype. For this purpose, we down-regulated RB18A/MED1 expression by transfecting melanoma cells with a RB18A/MED1 small interfering RNA (siRNA), specific to the 3'-untranslated region of native RB18A/MED1 RNA, already demonstrated to inhibit specifically RB18A/MED1 protein expression. A nonspecific (scrambled) siRNA was used as control. This RB18A/MED1 siRNA did not modify the expression of cathepsin L forms or lamin A/C, nor the secretion of procathepsin L and MMP2 in transfected cells. Analysis using a microarray membrane with 113 cancer-related genes, western blot and specific tests, demonstrated that RB18A/MED1 knockdown significantly inhibits tissue inhibitor of metalloproteinase-3 expression, and increases uPAR expression, two genes well known to be involved in melanoma cell invasion, through modifications of the tumor microenvironment. Indeed, RB18A/MED1 knockdown in melanoma cells in vitro increased their invasive properties, without modification of cell proliferation. Furthermore, RB18A/MED1 knockdown in vivo switched melanoma phenotype from non to strongly-tumorigenic in nude mice. Our data thus demonstrated for the first time that a decrease of RB18A/MED1 expression in human melanoma cells increases their tumorigenic phenotype.
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Dates and versions

inserm-03738131 , version 1 (25-07-2022)

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Jean de la Croix Ndong, Didier Jean, Nathalie Rousselet, Raymond Frade. Down-regulation of the expression of RB18A/MED1, a cofactor of transcription, triggers strong tumorigenic phenotype of human melanoma cells. International Journal of Cancer, 2009, 124 (11), pp.2597-2606. ⟨10.1002/ijc.24253⟩. ⟨inserm-03738131⟩

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