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Overexpression of cyclooxygenase‐2 in NCI‐H292 human alveolar epithelial carcinoma cells: Roles of p38 MAPK, ERK‐1/2, and PI3K/PKB signaling proteins

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. J. Cell. Biochem. 112: 3015–3024, 2011. © 2011 Wiley‐Liss, Inc.