Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids

Transcriptional Induction of Mitogen-activated Protein Kinase Phosphatase 1 by Retinoids

“…7D, RAR␣ antagonist ER50891 attenuated the t-RA-induced MKP-1 expression. RAR␥ antagonist MM11253 also modestly suppressed the t-RA-induced MKP-1 expression, although MM11253 per se slightly induced MKP-1 (data not shown), which may be due to its partial agonistic activity (33,34). In contrast, RAR␤ antagonist LE135 did not affect the t-RA-induced MKP-1 expression (Fig.…”

“…In some experiments, cells were costimulated with t-RA (0.5 -5 M) and H 2 O 2 (150 M). To examine roles of RAR and RXR in the regulation of MKP-1 by retinoids, the following agonists and antagonists were used: RAR agonist TTNPB (0.1-1 M) (24), RXR agonist AGN194204 (1 nM to 1 M) (25), RAR/RXR panagonist 9-cis-RA (1 nM to 10 M), RAR␣ agonist Am580 (0.01 nM to 0.01 M) (26), RAR␤ agonist CD2314 (0.1 nM to 1 M) (27), RAR␥ agonist CD666 (0.1 nM to 1 M) (26), RAR antagonist AGN193109 (0.1-5 M) (24), RXR antagonist HX531 (0.1-5 M) (28,29), RAR␣ antagonist ER50891 (0.1 M) (30), RAR␤ antagonist LE135 (0.1 M) (31,32), and RAR␥ antagonist MM11253 (also known as SR11253; 0.1 M) (33,34). Cells were pretreated with or without 10 -50 times higher concentrations of antagonists for 10 min and then stimulated with agonists for 1 h.…”

RARγ acts as a tumor suppressor in mouse keratinocytes

“…However, RARb is not expressed in epidermal keratinocytes, and our prior work suggests that RARg plays a pivotal role in retinoid-induced growth arrest in this cell type (Goyette et al, 2000). RARg has also been shown to mediate RA response of cell lines derived from head and neck SCCs and oral SCCs, where RARb expression has been silenced (Oridate et al, 1996;Le et al, 2000;Klaassen et al, 2001).…”

Genomics of Smoking Exposure and Cessation: Lessons for Cancer Prevention and Treatment

“…Elimination of retinal as retinol prevents the conversion of retinal to retinoic acid. Retinoic acid is a ligand for retinoid acid receptor and retinoid X receptor, and activation of these nuclear receptors leads to cell differentiation (41). If retinoid acid receptor and retinoid X receptor are deprived of their ligand, this could lead to a pro-proliferative response.…”