Abstract:
:Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-beta2 (RAR-beta2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-beta2. There was not a strict correlation between DNA methylation of RAR-beta gene and its expression. There was no difference in global and RARbeta 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-beta gene promoter was higher in cells expressing RAR-beta2. 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-beta2. Treatment of WM1366 melanoma cells with 5-aza 2'-deoxycytidine reactivated RAR-beta2 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-beta2 in some melanoma cells and pan-acetylation of H3 likely plays a permissive role in expression of RAR-beta2.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Fan J,Eastham L,Varney ME,Hall A,Adkins NL,Chetel L,Sollars VE,Georgel P,Niles RMdoi
10.1111/j.1755-148X.2010.00702.xsubject
Has Abstractpub_date
2010-06-01 00:00:00pages
419-29issue
3eissn
1755-1471issn
1755-148Xpii
PCR702journal_volume
23pub_type
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