Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand, modulates the E-cadherin/beta-catenin system in a human pancreatic cancer cell line, BxPC-3.
Activation of peroxisome proliferator-activated receptor (PPAR)-gamma induces terminal differentiation and growth inhibition associated with G1 cell cycle arrest in some cancer cells. The multifunctional molecule beta-catenin performs important roles in intercellular adhesion and signal transduction. However, no report has focused on actions of PPAR-gamma in regulating the E-cadherin/beta-catenin system. We examined whether thiazolidinedione (TZD), a potent PPAR-gamma ligand, could modulate the E-cadherin/beta-catenin system in a human pancreatic cancer cell line, BxPC-3, that has been found to express PPAR-gamma. According to Western blotting, TZD markedly increased differentiation markers including E-cadherin and carcinoembryonic antigen, while beta-catenin did not change significantly. In untreated cells, fluorescence immunostaining demonstrated beta-catenin predominantly in the cytoplasm and/or nucleus; in TZD-treated cells, beta-catenin localization had dramatically shifted to the plasma membrane, in association with increased E-cadherin at this site. Thus, a PPAR-gamma ligand appears to participate not only in induction of differentiation in pancreatic cancer cells, but also in the regulation of the E-cadherin/beta-catenin system. Such ligands may prove clinically useful as cytostatic anticancer agents.
Ohta
Tetsuo
T
Department of Surgery II, School of Medicine, Kanazawa University, Kanazawa 920-0934, Japan. ohtat@surg2.m.kanazawa-u.ac.jp
Elnemr
Ayman
A
Yamamoto
Miyuki
M
Ninomiya
Itasu
I
Fushida
Sachio
S
Nishimura
Gen-Ichi
G
Fujimura
Takashi
T
Kitagawa
Hirohisa
H
Kayahara
Masato
M
Shimizu
Koichi
K
Yi
Shuangqin
S
Miwa
Koichi
K
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008024:Ligands; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011233:Precipitin Tests; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D002272:Carcinoembryonic Antigen; D003598:Cytoskeletal Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C089946:2,4-thiazolidinedione