title: Potentiation of tumor formation by topical administration of 15-deoxy-delta12,14-prostaglandin J2 in a model of skin carcinogenesis.
abstract: The effect of prostaglandins on the development of papillomas has been investigated in mice receiving prostaglandins E2 (PGE2) or the cyclopentenone 15-deoxy-delta(12,14)-PGJ2 (15dPGJ2) topically, using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced tetradecanoylphorbol acetate (TPA)-promoted model of skin carcinogenesis. The presence of 15dPGJ2 during DMBA and TPA treatment inhibited apoptosis and increased the rate, number, size and vascularization of the papillomas, some of them progressing into carcinomas. Moreover, skin sections from mice treated for one week with DMBA and 15dPGJ2 showed a much reduced rate of apoptotic cells, and an enhanced expression of vascular epithelial growth factor when compared with animals receiving DMBA, with or without PGE2. The analysis of molecular events in the MCA3D keratinocyte cell line showed that 15dPGJ2 activated Ras and improved cell viability by inhibiting DMBA-dependent apoptosis. In addition to this, cell adhesion was impaired in MCA3D keratinocytes co-treated with 15dPGJ2 and DMBA, at the same time when the expression of cyclooxygenase-2 (COX-2) was observed under these conditions. These effects mediated by 15dPGJ2 might contribute to understand the role of COX-2 metabolites in carcinogenesis, leading to an increase of cell viability after mutagenic injury and therefore in the progression of tumors.
authors.affiliation: Instituto de Bioquímica, CSIC-UCM, 28040 Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Millán
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.forename: Héctor
authors.initials: H
authors.lastname: Peinado
authors.forename: Natasha
authors.initials: N
authors.lastname: Zarich
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stamatakis
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez-Sala
authors.forename: José M
authors.initials: JM
authors.lastname: Rojas
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage; D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000008:administration & dosage; D002471:Cell Transformation, Neoplastic; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D004347:Drug Interactions; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D010212:Papilloma / Q000139:chemically induced* / Q000503:physiopathology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002273:Carcinogens; D007155:Immunologic Factors; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2; D015230:Prostaglandin D2