Reduced heterochromatin protein 1-beta (HP1beta) expression is correlated with increased invasive activity in human melanoma cells.

Heterochromatin protein 1 (HP1) is associated with heterochromatin formation and the regulation of gene expression. In this study, we demonstrated that decreased HP1beta, but not HPla, mRNA and protein expression, correlates with invasive potential in five human melanoma cell lines, and we used immunohistochemistry to confirm that HP1beta expression is suppressed during melanoma progression. HPIP levels are decreased in (V600E)B-RAF-transformed mouse melanocytes, suggesting that HP1beta-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 HP1beta 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 HPIbeta down-regulation, which causes epigenetic gene regulation associated with melanoma progression.