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Molecular Biology

Lung Neoplasms

Articles 1 - 4 of 4

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

Peroxisome Proliferator-Activated Receptor Ligand Mcc-555 Suppresses Intestinal Polyps In Apcmin/+ Mice Via Extracellular Signal-Regulated Kinase And Peroxisome Proliferator-Activated Receptor-Dependent Pathways, K Yamaguchi, Maria Cekanova, Michael Mcentee, J Yoon, S Fischer, I Renes, I Van Seungnigen, Seung Baek Oct 2010

Peroxisome Proliferator-Activated Receptor Ligand Mcc-555 Suppresses Intestinal Polyps In Apcmin/+ Mice Via Extracellular Signal-Regulated Kinase And Peroxisome Proliferator-Activated Receptor-Dependent Pathways, K Yamaguchi, Maria Cekanova, Michael Mcentee, J Yoon, S Fischer, I Renes, I Van Seungnigen, Seung Baek

Maria Cekanova MS, RNDr, PhD

A large body of studies has suggested that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, such as thiazolidinedione, are potent candidates for chemopreventive agents. MCC-555 is a PPARgamma/alpha dual agonist and has been shown previously to induce apoptosis in vitro; however, the molecular mechanisms by which MCC-555 affects antitumorigenesis in vivo are poorly understood. In this study, we explored the antitumorigenic effects of MCC-555 both in cell culture and in Apc-deficient mice, an animal model for human familial adenomatous polyposis. MCC-555 increased MUC2 expression in colorectal and lung cancer cells, and treatment with the PPARgamma antagonist GW9662 revealed that MUC2 ...


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


Peroxisome Proliferator-Activated Receptor Ligand Mcc-555 Suppresses Intestinal Polyps In Apcmin/+ Mice Via Extracellular Signal-Regulated Kinase And Peroxisome Proliferator-Activated Receptor-Dependent Pathways, K Yamaguchi, Maria Cekanova, Michael Mcentee, J Yoon, S Fischer, I Renes, I Van Seungnigen, Seung Baek Aug 2008

Peroxisome Proliferator-Activated Receptor Ligand Mcc-555 Suppresses Intestinal Polyps In Apcmin/+ Mice Via Extracellular Signal-Regulated Kinase And Peroxisome Proliferator-Activated Receptor-Dependent Pathways, K Yamaguchi, Maria Cekanova, Michael Mcentee, J Yoon, S Fischer, I Renes, I Van Seungnigen, Seung Baek

Seung J Baek

A large body of studies has suggested that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, such as thiazolidinedione, are potent candidates for chemopreventive agents. MCC-555 is a PPARgamma/alpha dual agonist and has been shown previously to induce apoptosis in vitro; however, the molecular mechanisms by which MCC-555 affects antitumorigenesis in vivo are poorly understood. In this study, we explored the antitumorigenic effects of MCC-555 both in cell culture and in Apc-deficient mice, an animal model for human familial adenomatous polyposis. MCC-555 increased MUC2 expression in colorectal and lung cancer cells, and treatment with the PPARgamma antagonist GW9662 revealed that MUC2 ...


Epigallocatechin-3-Gallate Inhibits Interleukin-1beta-Induced Muc5ac Gene Expression And Muc5ac Secretion In Normal Human Nasal Epithelial Cells, H Kim, S Park, S Park, U Moon, B Lee, S Yoon, J Lee, Seung Baek, J Yoon Jul 2008

Epigallocatechin-3-Gallate Inhibits Interleukin-1beta-Induced Muc5ac Gene Expression And Muc5ac Secretion In Normal Human Nasal Epithelial Cells, H Kim, S Park, S Park, U Moon, B Lee, S Yoon, J Lee, Seung Baek, J Yoon

Seung J Baek

It has been reported that the proinflammatory cytokine interleukin-1beta (IL-1beta) induces mucus hypersecretion in normal human nasal epithelial (NHNE) cells and that the MAP kinase pathway may be an important signal pathway in IL-1beta-induced MUC5AC gene expression. Green tea (Camellia sinensis) polyphenols are potent anti-inflammatory agents and have been shown to inhibit inflammation in tumor cell lines and cultured respiratory epithelial cells. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1beta-induced MUC5AC gene expression and secretion in NHNE cells. After cells had been treated with IL-1beta (10 ng/ml) and pretreated with EGCG ...