Silencing and re-expression of retinoic acid receptor beta2 in human melanoma.

Pigment Cell Melanoma Res. 2010 Jun;23(3):419-29.
Fan J, Eastham L, Varney ME, Hall A, Adkins NL, Chetel L, Sollars VE,Georgel P, Niles RM.
Pigment Cell Melanoma Res. 2010 Jun;23(3):419-29.
Molte cellule di melanoma (WM1366) sono resistenti agli effetti anti-proliferativi dell'acido all-trans retinoico (ATRA). Il recettore beta2 dell'acido retinoico (RAR-beta2) media l'inibizione alla crescita di ATRA.

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.