title: Inhibitory effect of PPARγ on NR0B1 in tumorigenesis of lung adenocarcinoma.
abstract: NR0B1, an orphan nuclear receptor, is expressed in side population cells and its knockdown reduces tumorigenic and anti-apoptotic potential in lung adenocarcinoma. Peroxisome proliferator-activated receptor γ (PPARγ) is another member of the nuclear receptor family which induces apoptosis in lung cancer. The interaction of NR0B1 with PPARγ was examined. The transactivation ability of PPARγ was inhibited by NR0B1 in lung adenocarcinoma, and the N-terminal region of NR0B1 containing LxxLL motifs mediated its inhibition. Co-immunoprecipitation experiments revealed that this N-terminal region of NR0B1 was essential for the physical interaction with PPARγ. Aldehyde dehydrogenase (ALDH) activity and ALDH3A1 expression, which are correlated with tumorigenic potential of lung adenocarcinoma, increased when NR0B1 expression was induced, but its increase was inhibited by PPARγ overexpression. ALDH activity increased by treatment with PPARγ inhibitor, and the increase was further enhanced when the expression of NR0B1 was induced. Furthermore, the high NR0B1 and low PPARγ expression was a negative prognostic factor in Pathological-Stage IA clinical cases. These results indicate the reciprocal relationship between NR0B1 and PPARγ on the malignant grade of lung adenocarcinoma.
authors: Department of Pathology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
authors: Yoshiyuki
authors: Y
authors: Susaki
authors: Masayoshi
authors: M
authors: Inoue
authors: Masato
authors: M
authors: Minami
authors: Noriyoshi
authors: N
authors: Sawabata
authors: Yasushi
authors: Y
authors: Shintani
authors: Tomoyuki
authors: T
authors: Nakagiri
authors: Soichiro
authors: S
authors: Funaki
authors: Katsuyuki
authors: K
authors: Aozasa
authors: Meinoshin
authors: M
authors: Okumura
authors: Eiichi
authors: E
authors: Morii
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D020816:Amino Acid Motifs / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human; D047495:PPAR gamma; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase