Reduced heterochromatin protein 1-beta (HP1β) expression is correlated with increased invasive activity in human melanoma cells

2006 
Heterochromatin protein 1 (HP1) is associated with heterochromatin formation and the regulation of gene expression. In this study, we demonstrated that decreased HP1‚, but not HP1·, mRNA and protein expression, correlates with invasive potential in five human melanoma cell lines, and we used immunohistochemistry to confirm that HP1‚ expression is suppressed during melanoma progression. HP1‚ levels are decreased in V600E B-RAF-transformed mouse melanocytes, suggesting that HP1‚-mediated suppressive mechanisms correlate with melanoma oncogenesis. Expression of microphthalmia associated-transcription factor (MITF), an important melanocyte differentiation factor, is reduced in melanoma, which is correlated with poor prognosis. In CRL1579, SK-MEL-28 and HMV-II human melanoma cells in which HP1‚ expression is reduced by RNAi, MITF RNA levels and invasiveness activities are differentially altered and are not correlated with each other. Our findings indicate that the V600E B-RAF mutation induces HP1‚ down-regulation, which causes epigenetic gene regulation associated with melanoma progression. Heterochromatin protein 1 (HP1) is associated with heterochromatin formation and plays many important roles in the regulation of gene expression. In Drosophila melanogaster, HP1 participates in a phenomenon known as position effect variegation, in which heritable gene suppression is caused by abnormal translocation in the proximity of heterochromatin
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