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Retinoids and skin: Microarrays shed new light on chemopreventive action of all‐trans retinoic acid
Author(s) -
Cheepala Satish B.,
Syed Zanobia,
Trutschl Marjan,
Cvek Urska,
Clifford John L.
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20346
Subject(s) - retinoic acid , mapk/erk pathway , biology , tretinoin , carcinogenesis , tumor promotion , retinoid , cancer research , signal transduction , mode of action , skin cancer , microarray analysis techniques , cancer , pharmacology , microbiology and biotechnology , gene , biochemistry , gene expression , genetics
Abstract Despite the use of retinoids in the clinic for many years, their mode of action in the prevention of skin cancer is still unclear. Recent microarray analyses of the chemopreventive effect of all‐trans retinoic acid (ATRA), one of the primary naturally occurring biologically active retinoids, in the two‐stage mouse skin chemical carcinogenesis model have provided novel insight into their action. Comparison of the gene expression profiles of control skin to skin subjected to the two‐stage protocol for 3 wk, with or without ATRA, has shown that approximately half of the genes regulated by 12‐ o ‐tetradecanoylphorbol‐13‐acetate (TPA) are oppositely regulated when ATRA is coadministered with TPA. It was further shown the Raf/Mek/Erk branch of mitogen‐activated protein (MAP) kinase pathway contains a disproportionate number of oppositely regulated genes, thereby implicating it as one of the key pathways involved in tumor promotion by TPA, that is blocked by ATRA. This result has pointed the way toward the detailed study of Raf/Mek/Erk pathway signaling in skin cancer development and its potential as a target pathway for chemoprevention by ATRA and other chemopreventive drugs. © 2007 Wiley‐Liss, Inc.