Effects of 8-methoxypsoralen and ultraviolet light A on EGF receptor (HER-1) expression.
Activation of psoralens by ultraviolet light irradiation at 308-400 nm (UVA) is used in the photochemical treatment of psoriasis. While the major effect of this activation is the formation of DNA adducts, it was recently demonstrated that psoralens can also bind to specific saturable high affinity cellular receptors, and that this is associated with inhibition of epidermal growth factor (EGF)-receptor binding. In view of these findings, we have examined whether 8-methoxy-psoralen (8-MOP) itself, or in combination with UVA, influences expression of the human EGF-receptor gene ("HER-1") in a human keratinocyte cell line. We have found that 8 MOP alone, and to a lesser extent UVA, induce a striking increase in cellular levels of HER-1 RNA. The combination of 8-MOP with UVA produces less induction of HER-1 RNA than that obtained with 8-MOP alone. We suggest, therefore, that this effect of 8-MOP is not due to DNA damage, but may reflect a separate effect of this compound on receptor-mediated signal transduction.
Yang
X Y
XY
Institute of Cancer Research, Columbia University, New York, NY 10032.
Ronai
Z A
ZA
Santella
R M
RM
Weinstein
I B
IB
D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007633:Keratins; D008730:Methoxsalen / Q000494:pharmacology*; D011701:PUVA Therapy; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014466:Ultraviolet Rays
D012333:RNA, Messenger; D007633:Keratins; D066246:ErbB Receptors; D008730:Methoxsalen