title: Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells.
abstract: Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-gamma) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-gamma in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1). PPAR-gamma was expressed and functional in both cell lines. Activation of PPAR-gamma with its specific ligands, troglitazone and 15-deoxy-delta 12,14-prostaglandin J2, inhibited cell growth in a dose-dependent manner through inducing G1 cell cycle arrest. P53 protein expression differed in OCUT-1 and in ACT-1, though the levels stayed constant irrespective of ligand exposure in both cell lines. In contrast, p21 and p27 proteins were induced in a dose-dependent manner in both situations. This study showed that PPAR-gamma ligands were able to induce growth suppression in anaplastic thyroid cancer cells via a p53-independent, but p21- and p27-dependent cytostatic pathway. These tumor-suppressive effects of PPAR-gamma may provide a novel approach to the treatment of anaplastic thyroid cancer.
authors.affiliation: Department of Surgical Oncology, Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Chung
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Onoda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Kana
authors.initials: K
authors.lastname: Ogisawa
authors.forename: Chiemi
authors.initials: C
authors.lastname: Takenaka
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yano
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hato
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D002453:Cell Cycle; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C058992:Tagln protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53