title: Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-kappaB activity in lung cancer cells.
abstract: Uteroglobin (UG, Clara cell secretory protein) is a steroid inducible, multifunctional protein that is secreted by the mucosal epithelia. UG has anti-proliferative and anti-metastatic effects in cancer cells. COX-2, which catalyzes the first step in the synthesis of prostanoids, has been shown to be overexpressed in tumors. This study investigated the effect of UG on the inhibition of COX-2 expression in lung cancer cells. The level of the COX-2 protein and its mRNA were decreased by UG, as demonstrated by Western blot and the RT-PCR, respectively. The EIA shows that UG suppressed PGE2 synthesis. Western blot showed that the NF-kappaB nuclear translocation was inhibited by the transduction of UG. In addition, an EMSA demonstrated the inhibition of the NF-kappaB-DNA binding by UG. The luciferase assay showed that UG also inhibited the NF-kappaB-mediated transcription activity. Furthermore, transfection of the lung cancer cell lines with the COX-2 reporter gene constructs demonstrated that the transcription of COX-2 gene was suppressed by UG. These results show that the inhibition of COX-2 expression by UG transduction correlated with the suppression of NF-kappaB activity in the lung cancer cells. This suggests that UG have the possibility for the treatment of lung cancer.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Youngon-Dong, Chongno-Gu, Seoul 110-744, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Yoon
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Lim
authors.forename: Chul-Gyu
authors.initials: CG
authors.lastname: Yoo
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Shim
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D049109:Cell Proliferation; D051546:Cyclooxygenase 2; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014598:Uteroglobin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D016328:NF-kappa B; D014598:Uteroglobin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases