title: Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma.
abstract: Peroxisome proliferator-activated receptor gamma is a member of the nuclear receptor superfamily involved in adipocyte differentiation and glucose homeostasis. There is evidence that peroxisome proliferator-activated receptor gamma may also act as a tumor suppressor. Here, we demonstrate expression of peroxisome proliferator-activated receptor gamma in benign melanocytic naevi, different variants of primary cutaneous melanomas, and melanoma metastases. Peroxisome proliferator-activated receptor gamma protein and peroxisome proliferator-activated receptor gamma1 mRNA were also detected in human melanoma cell lines. The peroxisome proliferator-activated receptor gamma specific agonists 15-deoxy-Delta12,14-prostaglandin J2, troglitazone, and rosiglitazone dose-dependently inhibited cell proliferation in four melanoma cell lines, whereas a specific agonist of peroxisome proliferator-activated receptor alpha had no such effect. At a concentration of 50 microM rosiglitazone, the most potent peroxisome proliferator-activated receptor gamma agonist tested suppressed cell growth by approximately 90%. Apoptosis could be induced in melanoma cell lines by incubation with tumor-necrosis-factor-related apoptosis-inducing ligand. In contrast, the growth inhibitory effect of peroxisome proliferator-activated receptor gamma activation was independent of apoptosis and seemed to occur primarily through induction of cell cycle arrest. Our data indicate that melanoma cell growth may be modulated through peroxisome proliferator-activated receptor gamma.
authors.affiliation: Department of Dermatology, Georg-August University Göttingen, Germany.
authors.forename: Rotraut
authors.initials: R
authors.lastname: Mössner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schulz
authors.forename: Ullrich
authors.initials: U
authors.lastname: Krüger
authors.forename: Peter
authors.initials: P
authors.lastname: Middel
authors.forename: Sven
authors.initials: S
authors.lastname: Schinner
authors.forename: László
authors.initials: L
authors.lastname: Füzesi
authors.forename: Christine
authors.initials: C
authors.lastname: Neumann
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008545:Melanoma; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D012878:Skin Neoplasms; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000970:Antineoplastic Agents; D002839:Chromans; D005343:Fibrinolytic Agents; D007155:Immunologic Factors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077288:Troglitazone; D015230:Prostaglandin D2