Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-kappaB activity in lung cancer cells.
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.
Yoon
Jung Min
JM
Department of Internal Medicine, Seoul National University College of Medicine, 28 Youngon-Dong, Chongno-Gu, Seoul 110-744, Korea.
Lim
Jae-Jun
JJ
Yoo
Chul-Gyu
CG
Lee
Choon-Taek
CT
Bang
Yung-Jue
YJ
Han
Sung Koo
SK
Shim
Young-Soo
YS
Kim
Young Whan
YW
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*
D008565:Membrane Proteins; D016328:NF-kappa B; D014598:Uteroglobin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases