Retinoic acid antagonizes basal as well as coal tar and glucocorticoid-induced cytochrome P4501A1 expression in human skin.
Cytochrome P4501A1 is known to be expressed in skin and thus has been implicated in the pathogenesis of skin cancer due to certain environmental carcinogens. Retinoic acid (RA) has been used in chemoprevention of certain skin and other epithelial cancers. Therefore, we used Northern and Western analysis to determine the effect of externally applied RA on basal P4501A1 expression. RA reduced basal levels of P4501A1 mRNA and protein by 68 (n = 14, P = 0.005) and 75% (n = 7, P = 0.04) respectively. RA application also reduced basal levels of P4501A2 (another P4501A1 subfamily member) mRNA by 93% (n = 7, P = 0.001) as determined by reverse transcription-polymerase chain reaction. Interestingly, P4501A1 mRNA expression induced by coal tar or glucocorticoid (clobetasol) was reduced 46 (n = 10, P = 0.003) and 69% (n = 5, P < 0.05) respectively by RA co-application. Downregulation of basal P4501A1 expression and antagonism of coal tar mediated P4501A1 induction by RA may be a mechanism involved in chemo-prevention of skin and other epithelial cancer by RA.
Li
X Y
XY
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109-0314.
Aström
A
A
Duell
E A
EA
Qin
L
L
Griffiths
C E
CE
Voorhees
J J
JJ
D000328:Adult; D002478:Cells, Cultured; D002990:Clobetasol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003033:Coal Tar / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D012333:RNA, Messenger; D014212:Tretinoin; D003033:Coal Tar; D003577:Cytochrome P-450 Enzyme System; D002990:Clobetasol