Abstract
Heterochromatin protein 1 (HP1) is associated with heterochromatin formation and the regulation of gene expression. In this study, we demonstrated that decreased HP1β, but not HP1α, mRNA and protein expression, correlates with invasive potential in five human melanoma cell lines, and we used immunohistochemistry to confirm that HP1β expression is suppressed during melanoma progression. HP1β levels are decreased in V600EB-RAF-transformed mouse melanocytes, suggesting that HP1 β-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 HP1β 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 V600EB-RAF mutation induces HP1β down-regulation, which causes epigenetic gene regulation associated with melanoma progression.
- Heterochromatin protein 1 beta (HP1β)
- V600EB-RAF mutation
- microphthalmia associated-transcription factor (MITF)
- malignant melanoma
- invasion
- metastasis
- RNAi
Footnotes
- Received June 9, 2006.
- Accepted August 18, 2006.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved