title: Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone.
abstract: Nuclear receptor subfamily 1, group I, member 3 (NR1I3) is reported to be a possible novel therapeutic target for some cancers, including lung, brain and hematopoietic tumors. Here, we characterized expression of NR1I3 in a mouse model of lung carcinogenesis induced by 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK), the most potent tobacco carcinogen. Lung tumors were collected from mice treated with NNK (400 mg/kg) and euthanized after 52 weeks. Benign and malignant lesions were formalin-fixed and paraffin-embedded for histology and immunohistochemistry, with samples snap-frozen for mRNA analysis. Immunohistochemically, we found that most macrophages and type I and II pneumocytes expressed NR1I3, whereas fibroblasts and endothelial cells were NR1I3-. Compared with benign lesions, malignant lesions had less NR1I3+ tumor cells. Gene expression analysis also showed an inverse correlation between NR1I3 mRNA expression and tumor size (P=0.0061), suggesting that bigger tumors expressed less NR1I3 transcripts, in accordance with our immunohistochemical NR1I3 tests. Our results indicate that NR1I3 expression decreased during progression of malignant lung tumors induced by NNK in mice.
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: H
authors.initials: H
authors.lastname: Fukumasu
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: Y G
authors.initials: YG
authors.lastname: Cordeiro
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: A L
authors.initials: AL
authors.lastname: Rochetti
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: C N
authors.initials: CN
authors.lastname: Barra
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: T S
authors.initials: TS
authors.lastname: Sámora
authors.affiliation: Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP, Brasil.
authors.forename: R F
authors.initials: RF
authors.lastname: Strefezzi
authors.affiliation: Laboratório de Oncologia Experimental e Comparada, Departmento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: M L Z
authors.initials: ML
authors.lastname: Dagli
mesh_terms: D000818:Animals; D000090702:Constitutive Androstane Receptor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental; D009602:Nitrosamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: D000090702:Constitutive Androstane Receptor; D009602:Nitrosamines; C000716328:Nr1i3 protein, mouse; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone