Both SCGB3A2 and NKX2-1 are expressed in airway epithelial cells and the latter also in alveolar Type II cells. NKX2-1 has been used clinically for the definitive diagnosis of human pulmonary tumors, particularly non-small cell lung cancer. Recently, the expression of SCGB3A2 was reported in human carcinomas, suggesting the use of this protein as a tumor marker. We used twenty eight lung tumors from aging B6;129 mice and nine lung adenocarcinomas from CC10TAg transgenic mice that express SV40 large T antigen under the mouse SCGB1A1 (CC10) gene promoter, which were subjected to histopathological and immunohistochemical analyses to determine the expression of NKX2-1 and SCGB3A2. NKX2-1 was expressed in all types of tumors albeit more focally in carcinomas. In contrast, SCGB3A2, normally expressed in Clara cells, was negative in Type II cell hyperplasias and adenomas. However, it was expressed in alveolar Type II cell carcinomas and Clara cell adenocarcinomas. In these carcinomas, SCGB3A2 expression was observed in the portion of the tumor where NKX2-1 expression was reduced or almost abolished. As a comparison, the expression of SCGB3A2 and NKX2-1 from twenty-three human non-small cell lung carcinoma specimens was also examined. The results demonstrated that SCGB3A2 is a useful marker for diagnosis of pulmonary tumors both in mice and humans. We found that the expression of SCGB3A1 and SCGB3A2 are bidirectionally regulated by oncostatin M (OSM) when examined in a mouse transformed Clara cell line (mtCC);SCGB3A1 is up-regulated by OSM while SCGB3A2 is down-regulated in a time and dose-dependent manner. OSM-activated STAT3/5, through binding to the STAT-binding element located at -201 to -209 bp in the mouse SCGB3A1 gene promoter, and the ERK-and p38-MAPK pathways are responsible for the OSM-induced up-regulation of SCGB3A1 expression. On the other hand, the -113 to -273 bp region in the SCGB3A2 promoter appears to be responsible for the OSM induced down-regulation of the gene. No significant differences in the levels or patterns of specific DNA-binding proteins were found in the -113 to -273 bp region as determined by electrophoretic mobility shift assays. Neither the ERK- nor p38-MAPK pathways were involved in the OSM-induced reduction of SCGB3A2 promoter activity. These results suggest that OSM-induced suppression of SCGB3A2 expression is an indirect effect of OSM. Expression of the Clara cell marker, CYP2F2, was markedly decreased upon OSM treatment in parallel with the decrease of SCGB3A2 expression in mtCC cells. The differential regulation of SCGB3A1 and SCGB3A2 gene expression by OSM may explain the unique functions of these genes in the lung.

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Kim, Jung-Hwan; Yamaori, Satoshi; Tanabe, Tomotaka et al. (2017) Lack of epithelial PPAR? causes cystic adenomatoid malformations in mouse fetal lung. Biochem Biophys Res Commun 491:271-276
Tanaka, Naoki; Aoyama, Toshifumi; Kimura, Shioko et al. (2017) Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol Ther :
Yoneda, Mitsuhiro; Xu, Lei; Kajiyama, Hiroaki et al. (2016) Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice. Int Arch Allergy Immunol 171:36-44
Naizhen, Xu; Linnoila, R Ilona; Kimura, Shioko (2016) Co-expression of Achaete-Scute Homologue-1 and Calcitonin Gene-Related Peptide during NNK-Induced Pulmonary Neuroendocrine Hyperplasia and Carcinogenesis in Hamsters. J Cancer 7:2124-2131
Xu, Ming-Jiang; Cai, Yan; Wang, Hua et al. (2015) Fat-Specific Protein 27/CIDEC Promotes Development of Alcoholic Steatohepatitis in Mice and Humans. Gastroenterology 149:1030-41.e6
Yoneda, Mitsuhiro; Molinolo, Alfredo A; Ward, Jerrold M et al. (2015) A Simple Device to Rapidly Prepare Whole Mounts of the Mouse Intestine. J Vis Exp :e53042
Cai, Yan; Kimura, Shioko (2015) Secretoglobin 3A2 Exhibits Anti-Fibrotic Activity in Bleomycin-Induced Pulmonary Fibrosis Model Mice. PLoS One 10:e0142497
Kurotani, Reiko; Shima, Reika; Miyano, Yuki et al. (2015) SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation. Acta Histochem Cytochem 48:61-8
Cai, Yan; Yoneda, Mitsuhiro; Tomita, Takeshi et al. (2015) Transgenically-expressed secretoglobin 3A2 accelerates resolution of bleomycin-induced pulmonary fibrosis in mice. BMC Pulm Med 15:72
Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro et al. (2014) Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer. J Pharmacol Exp Ther 351:559-67

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