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Inhibition of epidermal growth factor receptor tyrosine kinase activity in A431 human epidermoid cells following psoralen/ultraviolet light treatment.
Mermelstein, F H; Abidi, T F; Laskin, J D.
Affiliation
  • Mermelstein FH; Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey, Piscataway 08854.
Mol Pharmacol ; 36(6): 848-55, 1989 Dec.
Article in En | MEDLINE | ID: mdl-2557535
ABSTRACT
One of the more prominent clinical treatments for skin diseases such as psoriasis and vitiligo involves the use of a combination of psoralens and UV light, a procedure referred to as PUVA chemotherapy. This drug regimen markedly alters epidermal cell growth and differentiation. In many cell types, an early cellular event following treatment of cells with PUVA is inhibition of binding of epidermal growth factor (EGF) to its receptor. To examine the mechanism underlying this effect, we used A431 cells, a human epidermal cell line known to express large numbers of EGF receptors. We found that exposure of A431 cells to PUVA caused a dramatic inhibition of EGF-stimulated EGF receptor tyrosine kinase activity. Inhibition required intact cells and did not appear to be mediated by protein kinase C, because this inhibition was apparent in cells in which the enzyme was down-regulated by phorbol ester pretreatment and in cells treated with inhibitors of protein kinase C. Inhibition of tyrosine kinase activity by PUVA was distinct from other inhibitors of EGF receptor function in that it was associated with a rapid increase in the amount of phosphate incorporated into serine residues of the EGF receptor. This suggested that PUVA-induced serine phosphorylation may mediate EGF receptor kinase activity. These results demonstrate that alterations in EGF receptor function may contribute to the therapeutic efficacy of PUVA in photo-chemotherapy.
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Collection: 01-internacional Database: MEDLINE Main subject: PUVA Therapy / Protein-Tyrosine Kinases / ErbB Receptors Limits: Humans Language: En Journal: Mol Pharmacol Year: 1989 Type: Article
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Collection: 01-internacional Database: MEDLINE Main subject: PUVA Therapy / Protein-Tyrosine Kinases / ErbB Receptors Limits: Humans Language: En Journal: Mol Pharmacol Year: 1989 Type: Article