title: Inhibition of peroxisome proliferator-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties.
abstract: Esophageal cancer is difficult to treat because of its rapid progression, and more effective therapeutic approaches are needed. The PPARgamma is a nuclear receptor superfamily member that is expressed in many cancers. PPARgamma expression is a feature of esophageal cancer cell lines, and in the present investigation, the PPARgamma antagonists T0070907 and GW9662 could induce loss of invasion but could not induce growth reduction or apoptosis at low concentrations (< 10 mM). A high concentration of antagonists (50 microM) inhibited cell growth and induced apoptosis, but these effects did not explain our result at the low concentration. Morphological change, decreased expression of the cell signaling pathway and inhibition of cancer cell invasion were observed in the low concentration. This suggested that PPARgamma antagonists inhibited esophageal cancer cell invasion as well as cell adherence, most likely due to alteration in the FAK-MAPK pathway, and this was independent of apoptosis. These results suggested that PPARgamma plays an important role in cancer cell invasion and that it might be a novel target for therapy of esophageal cancer.
authors.affiliation: Gastroenterology Division, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kouji
authors.initials: K
authors.lastname: Fujita
authors.forename: Toshio
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yonemitsu
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomimoto
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ikeda
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Masuda
authors.forename: Katherine
authors.initials: K
authors.lastname: Schaefer
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Saubermann
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Saitoh
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000199:Actins / Q000187:drug effects; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000199:Actins; D000813:Anilides; D001549:Benzamides; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases