The cleavage fragment of retinoid X receptor-alpha ligand binding domain inhibits radiosensitization by retinoic acid

Oncol Rep. 2010 Jun;23(6):1715-20.
Cho YM, Yang AH, Kim BY, Han YH.
Oncol Rep. 2010 Jun;23(6):1715-20.
Il retinoide X-recettore alfa (alfa RXR) e il dominio di legame del ligando (LBD) possono agire come regolatori negativi dell'effetto radiosensibilizzante dell'acido retinoico (RA), limitando la risposta biologica dell'acido retinoico recettore-gamma (RAR gamma).
RXR alfa/RAR gamma.

Retinoid X receptor-alpha (RXR alpha) fragments are known to be produced in some cancer cells by proteolytic cleavage. Previous finding that ligand binding domain (LBD) fragment of RXR alpha specifically inhibits retinoic acid receptor-gamma (RAR gamma) activity led us to investigate the functional role of RXR alpha LBD fragment in radiosensitization by retinoic acid (RA). Ectopic expression of RXR alpha LBD fragment in cells that do not have a detectable endogenous RXR alpha LBD fragment, blocked synergistic radiosensitizing action of RA, as determined by growth inhibition, cell death and colony formation assays. However, H460 cell, which has an endogenous RXR alpha LBD fragment, was not radiosensitized by RA regardless of the ectopic RXR alpha
LBD fragment expression. These results were paralleled with the pattern of p21 Waf1/Cip1 induction by the treatment of RA in combination with ionizing radiation (IR). Taken together, we hypothesize that the RXR alpha LBD fragment may act as a negative regulator of radiosensitizing effect of RA by restricting the RAR gamma-mediated biological response to RA.