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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2002 Dec;93(12):1358–1365. doi: 10.1111/j.1349-7006.2002.tb01245.x

Peroxisome Proliferator‐activated Receptor Gamma Activation Induces Cell Cycle Arrest via the p53‐independent Pathway in Human Anaplastic Thyroid Cancer Cells

Sung Hwa Chung 1, Naoyoshi Onoda 1,2,✉, Tetsuro Ishikawa 1, Kana Ogisawa 1, Chiemi Takenaka 1,2, Yoshihisa Yano 3, Fumihiko Hato 4, Kosei Hirakawa ✉
PMCID: PMC5926938  PMID: 12495476

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‐γ) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR‐γ in anaplastic thyroid cancer cell lines (OCUT‐1, ACT‐1). PPAR‐γ was expressed and functional in both cell lines. Activation of PPAR‐γ with its specific ligands, troglitazone and 15‐deoxy‐Δ12, 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‐γ 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‐γ may provide a novel approach to the treatment of anaplastic thyroid cancer.

Keywords: PPAR‐γ, Anaplastic thyroid cancer, p53, p21, p27

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