Retinoid, RARa-selective

The first RARa-selective retinoids identified were the Shudo group s 4-[(5,6,7,8-tetrahy-dro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid (Am80) and 4-[(5,6,7,8-tetra-... 

Figure 1. Concentration-dependent transcriptional activation of the retinoic acid receptor subtypes a, p, and yon the (TREpal)2-tfc-CAT reporter construct in CV-1 cells by (A) RARa-selective retinoids Am580 (RARa, RARp, RARy A) and Am80 (RARa, O RARp, RARy A), and (B) RARy-selective retinoids SRI 1254 (RARa, RARP, RARy A) and AHPN (RARa, O RARp, RARy A).

Because the skin contains RARa and RARy proteins, with the latter predominating (1 6) [12], research is devoted to establishing the predominant signalling pathway in the skin in order to develop more effective dermatological agents [127]. Yu et al. [59] reported that RARa-selective retinoids had greater potency than RARy-selective retinoids at reducing utricule size in... 

Roy, B., Taneja, R., and Chambon, P. (1995). Synergistic activation of retinoic acid (RA)-re-sponsive genes and induction of embryonal carcinoma ceU differentiation by an RA receptor a (RARa)-, RARP-, or RARy-selective ligand in combination vdth a retinoid X receptor-specific ligand. Mol. Cell. Biol. 15, 6481-6487. 

To further complicate this biological-activity scheme, as well as the central importance observed for RARa and RARP in mediating RA activity in breast cancer, recent studies have demonstrated the relevance of the third member of the RAR family, RARy. This receptor also seems to play a role in controlling the growth of breast cancer cells [36], being elevated by RA treatment in several ER and ER" cells, concomitant of retinoid responsiveness [37]. These data are also confirmed by the retained biological activity of RARy-selective retinoids in comparison with RA, as observed by successive studies [38]. 

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