title: FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.
abstract: Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.
authors.affiliation: a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ;
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ;
authors.forename: Suni
authors.initials: S
authors.lastname: Lee
authors.affiliation: b Department of Biofunctional Chemistry, Division of Bioscience , Okayama University Graduate School of Natural Science and Technology , Okayama , Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.affiliation: a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ;
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai-Takei
authors.affiliation: a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ;
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: a Department of Hygiene , Kawasaki Medical School , Kurashiki , Japan ;
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001194:Asbestos / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology*; D008654:Mesothelioma / Q000139:chemically induced / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D000072224:Bcl-2-Like Protein 11; C085126:FOXO1 protein, human; D053222:Fas Ligand Protein; D000071161:Forkhead Box Protein O1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D001194:Asbestos
keywords: Asbestos; FoxO1; apoptosis; regulatory T-cell; transcription factor