title: Overexpression of cyclooxygenase-2 in NCI-H292 human alveolar epithelial carcinoma cells: roles of p38 MAPK, ERK-1/2, and PI3K/PKB signaling proteins.
abstract: Evidence suggests overexpression of COX-2 and its role in many human cancers, including lung. However, the regulatory mechanism underlying COX-2 overexpression in lung cancer is not fully understood. We herein investigated whether COX-2 is overexpressed in human airway cancer cell lines, including A549 (lung), Hep-2 (bronchial), and NCI-H292 (alveolar). When grown in cell culture medium containing 10% FBS (serum), of note, there was strong and transient induction of COX-2 protein and mRNA in NCI-H292 cells, but little or low COX-2 expression is seen in A549 or Hep-2 cells. Interestingly, strong and sustained activities of ERK-1/2, JNK-1/2, p38 MAPK, and PKB were also shown in NCI-H292 cells grown in presence of serum. Profoundly, results of pharmacological inhibition studies demonstrated that the serum-dependent COX-2 up-regulation in NCI-H292 cells is attributed to not only the p38 MAPK-, PI3K/PKB-, and ERK-1/2-mediated COX-2 transcriptional up-regulation but also the p38 MAPK- and ERK-1/2-mediated post-transcriptional COX-2 mRNA stabilization. Of further note, it was shown that the ERK-1/2 and PI3K/PKB (but not COX-2, p38 MAPK, and JNK-1/2) activities are necessary for growth of NCI-H292 cells. These findings collectively demonstrate for the first time that COX-2 expression is transiently up-regulated by serum addition in NCI-H292 cells and the serum-induced COX-2 expression is closely linked to the p38 MAPK-, ERK-1/2-, and PI3K/PKB-mediated COX-2 transcriptional and post-transcriptional up-regulation.
authors.affiliation: Department of Medical Genetic Engineering, Keimyung University School of Medicine, 1000 Dalgubeol-daero, Dalseo-gu, Daegu 704-701, Korea.
authors.forename: Suhaeng
authors.initials: S
authors.lastname: Sung
authors.forename: Yukyoung
authors.initials: Y
authors.lastname: Park
authors.forename: Jeong-Rang
authors.initials: JR
authors.lastname: Jo
authors.forename: Nak-Kyun
authors.initials: NK
authors.lastname: Jung
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Bae
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Keum
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Gy-Young
authors.initials: GY
authors.lastname: Park
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D055550:Protein Stability; D020871:RNA Stability; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases