Abstract:
: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.
journal_name
Oncol Repjournal_title
Oncology reportsauthors
Cho YM,Yang AH,Kim BY,Han YHdoi
10.3892/or_00000816subject
Has Abstractpub_date
2010-06-01 00:00:00pages
1715-20issue
6eissn
1021-335Xissn
1791-2431journal_volume
23pub_type
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