title: Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model.
abstract: Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising from mesothelial cells. Evidence suggests that the major pathology associated with asbestos-induced mesothelioma is local iron overload. In the present study, we induced iron-induced mesothelioma in rats based on previous reports. Ten Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum and tunica vaginalis. The tumor cells showed positive immunostaining for calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'-deoxyguanosine. In three of the five rats with mesothelioma, array-based comparative genomic hybridization analysis identified a common chromosomal deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene. Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1 gene expression was also reduced in three of four human malignant pleural mesothelioma cell lines compared with normal bronchial epithelial cells. Immunohistochemistry revealed that TBXAS1 expression was weakly positive and positive in five and three out of eight human malignant mesothelioma samples, respectively. In conclusion, TBXAS1 gene expression was downregulated in rats with iron-induced mesothelioma. The relationship between iron overload and TBXAS1 downregulation should be pursued further.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Minami
authors.affiliation: Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Isozaki
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Hospital, Okayama, Japan.|Department of Clinical Genomic Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Shinsuke
authors.identifier: http://orcid.org/0000-0001-8643-5037
authors.initials: S
authors.lastname: Hashida
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Harada
authors.affiliation: Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ochi
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Kadoaki
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Pathology, Okayama University Hospital, Okayama, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Hospital, Okayama, Japan.|Department of Clinical Genomic Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000235:genetics; D015536:Down-Regulation; D005290:Ferric Compounds; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006801:Humans; D007501:Iron / Q000633:toxicity*; D019190:Iron Overload / Q000235:genetics; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008654:Mesothelioma / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D000072260:RNA Splicing Factors; D051381:Rats; D017208:Rats, Wistar; D013930:Thromboxane-A Synthase / Q000235:genetics*; D000098853:Podoplanin
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D014408:Biomarkers, Tumor; D064032:Calbindin 2; D018797:Cell Cycle Proteins; D003849:Deoxyguanosine; D005290:Ferric Compounds; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D007501:Iron; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D013930:Thromboxane-A Synthase; C092025:Pdpn protein, rat; D000098853:Podoplanin; C419554:WTAP protein, human
keywords: Asbestos; TBXAS1; carcinogenesis; iron; malignant mesothelioma