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Silencing and re‐expression of retinoic acid receptor beta2 in human melanoma
Author(s) -
Fan Jun,
Eastham Linda,
Varney Melinda E.,
Hall Adam,
Adkins Nicolas L.,
Sollars Vincent E.,
Georgel Philippe,
Niles Richard M.
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00702.x
Subject(s) - trichostatin a , retinoic acid receptor , retinoic acid , retinoic acid receptor beta , histone deacetylase , retinoic acid receptor alpha , gene silencing , acetylation , cancer research , retinoic acid inducible orphan g protein coupled receptor , biology , retinoic acid receptor gamma , dna methylation , microbiology and biotechnology , histone deacetylase inhibitor , chemistry , histone , gene expression , biochemistry , gene
Summary Many melanoma cells are resistant to the anti‐proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor‐β2 (RAR‐β2) mediates the ATRA growth inhibition. We found a correlation between the anti‐proliferative activity of ATRA and expression of RAR‐β2. There was not a strict correlation between DNA methylation of RAR ‐β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan‐acetylation of H3 and H4 within the RAR‐β gene promoter was higher in cells expressing RAR‐β2. All trans retinoic acid treatment of responsive cells did not change pan‐acetylation of H3/H4, but addition of ATRA to non‐responsive cells increased H4 pan‐acetylation. Phytochemicals or the histone deacetylase inhibitor Trichostatin A did not restore expression of RAR‐β2. Treatment of WM1366 melanoma cells with 5‐aza 2′‐deoxycytidine reactivated RAR‐β2 gene expression and restored the ability of ATRA to further induce the expression of this gene. Therefore, promoter methylation is responsible for silencing of RAR‐β2 in some melanoma cells and pan‐acetylation of H3 likely plays a permissive role in expression of RAR‐β2.