Home
Resources
Publications
Cell Type and Gene-Specific Activity of the Retinoid Inverse Agonist AGN 193109: Divergent Effects From Agonist at Retinoic Acid Receptor Gamma in Human Keratinocytes

Cell Type and Gene-Specific Activity of the Retinoid Inverse Agonist AGN 193109: Divergent Effects From Agonist at Retinoic Acid Receptor Gamma in Human Keratinocytes

S M Thacher, S Nagpal, E S Klein, T Arefieg, G Krasinski, D DiSepio, C Agarwal, A Johnson, R L Eckert, R A Chandraratna

Cell Growth Differ. 1999 Apr;10(4):255-62.

PMID: 10319995

Abstract:

Retinoids are important regulators of epithelial differentiation. AGN 193109 is a high-affinity antagonist and inverse agonist for the nuclear retinoic acid receptors (RARs). Paradoxically, both AGN 193109 and retinoid agonists inhibit the expression of the differentiation marker MRP-8 in normal human keratinocytes (NHKs). TTNPB, an RAR agonist, and AGN 193109 mutually antagonize MRP-8 inhibition at both mRNA and protein levels. We find that this antagonism, which is greatest at an AGN 193109:TTNPB ratio of about 10:1, is absent when either compound is in significant excess. The potent RARalpha-specific agonist, AGN 193836, has no effect on MRP-8 regulation. These data indicate that inverse agonists and agonists suppress MRP-8 in NHKs through RARgamma using distinct and mutually inhibitory mechanisms. The activity of AGN 193109 on MRP-8 is cell type specific. In differentiating ECE16-1 cervical cells, TTNPB inhibits while AGN 193109 induces MRP-8 mRNA levels. The effect of AGN 193109 on genes inhibited by retinoid agonists in NHKs is also selective; expression of the differentiation markers transglutaminase 1 and keratin 6 is not down-regulated by AGN 193109 whereas stromelysin-1 expression is suppressed. These results show a complex gene and cell context-specific interplay between agonist and inverse agonist for the regulation of gene expression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP171746217	AGN 193109		171746-21-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: