Prostaglandin E2 reinforces the activation of Ras signal pathway in lung adenocarcinoma cells via EP3

[摘要]

Prostaglandin E₂ (PGE₂)-dependent effects on various cell responses are regulated by respective PGE₂ receptors (EP₁, EP₂, EP₃, EP₄) expressing in target cells. Alveolar type II cell (a main progenitor cell of lung adenocarcinoma) expressed only EP₄, while human lung adenocarcinoma cells (A549) expressed EP₃ as well as EP₄. An antagonistic effect of EP₃ against EP₄ through the modulation of cyclic AMP level is required for PGE₂-mediated activation of Ras signal pathway in A549 cells. These results suggest that the expression of EP₃ may be a critical factor for the PGE₂-mediated activation of Ras signal pathway in A549 cells.

[学科分类] 生物化学/生物物理

[关键词] Prostaglandin E2;Ras;Lung adenocarcinoma;Alveolar type II cell;cAMP;EP3;cAMP;cyclic AMP;NSCLC;non-small cell lung cancer;PGE2;prostaglandin E2;COX-2;cyclooxygenase-2;FCS;fetal calf serum;PTX;pertussis toxin;IBMX;isobutylmethylxanthine;Erk;extracellular signal-regulated kinase;Mek-P;phosphorylated Mek;Erk-P;phosphorylated Erk;G protein;heterotrimeric guanine nucleotide-binding regulatory protein;AC;adenylate cyclase;PKA;protein kinase A