MHC class I molecules act as tumor suppressor genes regulating the cell cycle gene expression, invasion, and intrinsic tumorigenicity of melanoma cells
Menée sur des lignées cellulaires de mélanome, cette étude suggère que les molécules du complexe majeur d'histocompatibilité de classe I sont susceptibles de jouer un rôle de suppresseur de tumeurs
The alteration of MHC class I (MHC-I) expression is a frequent event during cancer progression, allowing tumor cells to evade the immune system. We report that the loss of one MHC haplotype in human melanoma cells not only allowed them to evade immunosurveillance but also increased their intrinsic oncogenic potential. A second successive defect in MHC-I expression, MHC-I total downregulation, gave rise to melanoma cells that were more oncogenic per se in vivo and showed a higher proliferation rate and greater migratory and invasive potential in vitro. All of these processes were reversed by restoring MHC-I expression via HLA-A2 gene transfection. MHC-I cell surface expression was inversely correlated with intrinsic oncogenic potential. Modifications in the expression of various cell cycle genes were correlated with changes in MHC-I expression; the most important differences among the melanoma cell lines were in the transcriptional level of AP2-alpha, cyclin A1, and p21WAF1/CIP1. According to these results, altered MHC-I expression in malignant cells can directly increase their intrinsic oncogenic and invasive potential and modulate the expression of cell cycle genes. These findings suggest that HLA class I molecules may act directly as tumor suppressor genes in melanoma.
http://carcin.oxfordjournals.org/content/early/2012/01/04/carcin.bgr318.abstract