Identification of MAP kinase pathways involved in COX-2 expression following photofrin photodynamic therapy.
Photodynamic therapy (PDT) using the photosensitizer Photofrin is approved for the clinical treatment of solid tumors. PDT causes cytotoxic oxidative stress, but additionally induces prosurvival molecules such as cyclooxygenase-2 (COX-2). Combining PDT with COX-2 inhibitors increases the efficacy of in vivo treatment. Understanding mechanisms leading to prosurvival molecule induction is relevant to the design of more effective treatments. Using COX-2 promoter constructs, transcription factor-binding assays, identification of protein kinase activation, and inhibitors of transcription factor binding we were able to determine that COX-2 expression following PDT involves the p38 MAP kinase pathway.
Luna
Marian
M
Departments of Pediatrics and Radiation Oncology, Keck School of Medicine, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
Ferrario
Angela
A
Wong
Sam
S
Gomer
Charles J
CJ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects*; D008156:Luciferases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010778:Photochemotherapy; D010957:Plasmids / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D012313:RNA; D017323:Dihematoporphyrin Ether; D008156:Luciferases; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases