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Articles 1 - 5 of 5

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Signal Pathway Of 17Β-Estradiol–Induced Muc5b Expression In Human Airway Epithelial Cells, H Choi, Y Chung, H Kim, U Moon, Y Choi, I Van Seuringen, Seung Baek, H Yoon, J Yoon Dec 2008

Signal Pathway Of 17Β-Estradiol–Induced Muc5b Expression In Human Airway Epithelial Cells, H Choi, Y Chung, H Kim, U Moon, Y Choi, I Van Seuringen, Seung Baek, H Yoon, J Yoon

Seung J Baek

MUC5B is a major mucin of the human respiratory tract, and it is not clear how MUC5B expression is regulated in various airway diseases. The goal of this study was to determine the mechanisms by which 17β-estradiol induces MUC5B gene expression in airway epithelial cells. It was found that E2, a sex hormone, stimulates MUC5B gene overexpression by interaction with estrogen receptor {alpha} (ER{alpha}) and by acting through extracellular signal–regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK). Pretreatment with ER antagonist ICI 182,780 blocked both E2-induced ERK1/2-MAPK activation and MUC5B gene expression. It was ...


Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, M Cekanova, S Lee, M Sukhthankar, R Donnell, T Eling, S Fischer, Seung Baek Dec 2008

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, M Cekanova, S Lee, M Sukhthankar, R Donnell, T Eling, S Fischer, Seung Baek

Seung J Baek

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1(Tg+/FVB)). NAG-1(Tg+/FVB) mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice. Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore, significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention


Changes In Hepatic Gene Expression In Dogs With Experimentally Induced Nutritional Iron Deficiency, M Fry, C Kirk, J Liggett, G Daniel, Seung Baek, J Gouffon, P Chimakurthy, B Rekapalli Dec 2008

Changes In Hepatic Gene Expression In Dogs With Experimentally Induced Nutritional Iron Deficiency, M Fry, C Kirk, J Liggett, G Daniel, Seung Baek, J Gouffon, P Chimakurthy, B Rekapalli

Seung J Baek

BACKGROUND AND OBJECTIVE: We investigated hepatic gene expression in dogs with experimentally induced nutritional iron deficiency (ID). Our hypothesis was that ID would result in decreased hepcidin gene expression, and possibly in altered expression of other genes associated with iron metabolism. METHODS: Liver biopsies were collected from each of 3 dogs before induction of ID, at the point of maximal ID, and after resolution of ID. Using Affymetrix microarray technology and analytical tools specifically designed for microarray data, we identified genes that had at least a 2-fold change in expression in response to ID. Four genes were selected for further ...


The Cyclooxygenase Inhibitor Sulindac Sulfide Inhibits Ep4 Expression And Suppresses The Growth Of Glioblastoma Cells, A Kambe, H Yoshioka, H Kamitani, T Watanabe, Seung Baek, T Eling Dec 2008

The Cyclooxygenase Inhibitor Sulindac Sulfide Inhibits Ep4 Expression And Suppresses The Growth Of Glioblastoma Cells, A Kambe, H Yoshioka, H Kamitani, T Watanabe, Seung Baek, T Eling

Seung J Baek

EP4 expression in human glioblastoma cells correlates with growth on soft agar. The cyclooxygenase inhibitor sulindac sulfide first altered specificity protein-1 (Sp-1) and early growth response gene-1 expression, then increased the expression of nonsteroidal anti-inflammatory drug-activated gene 1 and activating transcription factor 3, and then decreased EP4 expression. EP4 suppression was dependent on blocking the Sp-1 binding sites in the human EP4 promoter. Mutation in the Sp-1 sites in EP4 altered the promoter activity and abolished sulindac sulfide effects. The inhibitory effect of sulindac sulfide on EP4 expression was reversed by PD98059, a mitogen-activated protein/extracellular signal-regulated kinase kinase-1/extracellular ...


A Reciprocal Relationship Exists Between Non-Steroidal Anti-Inflammatory Drug-Activated Gene-1 (Nag-1) And Cyclooxygenase-2, G Iguchi, K Chrysovergis, S Lee, Seung Baek, R Langenbach, T Eling Dec 2008

A Reciprocal Relationship Exists Between Non-Steroidal Anti-Inflammatory Drug-Activated Gene-1 (Nag-1) And Cyclooxygenase-2, G Iguchi, K Chrysovergis, S Lee, Seung Baek, R Langenbach, T Eling

Seung J Baek

Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) and COX-2 are involved in cellular processes such as inflammation, apoptosis, and tumorigenesis. To address the relationship between COX-2 and NAG-1 expression, we investigated the expression of NAG-1 and COX-2 in normal and tumor tissue from human patients, Apc(Min/+) mice, and COX-2(-/-) mice. While COX-2 expression is highly induced in tumor tissue, NAG-1 expression is reduced. Furthermore, PGE(2) reduces NAG-1 while celebrex induces NAG-1 expression. The results suggest that a possible inverse relationship exists between the expression of NAG-1 and COX-2 in tumor formation of colon tissue.