TY - JOUR T1 - cAMP-response element binding protein in KRAS-driven lung adenocarcinoma JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA522 VL - 48 IS - suppl 60 SP - PA522 AU - Georgia Giotopoulou AU - Nikolitsa Spiropoulou AU - Evanthia Tourkochristou AU - Ioannis Lilis AU - Nikolaos Kanellakis AU - Anthodesmi Krontira AU - Georgios Stathopoulos AU - Antonia Marazioti Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA522.abstract N2 - cAMP-response element binding protein (CREB) is an essential survival factor for normal respiratory epithelium, however, its role in lung cancer development has not been investigated. Our aim was to define the impact of CREB on KRAS-driven lung adenocarcinoma. Wild-type (W), conditional mutant KRAS-expressing (LSL.KRASG12D; K), and Creb1-deleted (Creb1 f/f; C) mice were intercrossed in all possible combinations, followed by intraperitoneal urethane or single intratracheal adenovirus (Ad)-Cre delivery.Conditional Creb1-deleted lung cancer cell lines (CCLC) were derived from the lungs of urethane- but not Ad-Cre-treated C mice.(Ad)-Cre-treated C mice were markedly protected from urethane-triggered lung tumorigenesis compared with W controls [lung tumor mass, median(95%CI), respectively: 1(5-11) and 24(19-45) μL; P<0.001] and (Ad)-Cre-treated KC mice developed significantly smaller lung tumors compared with K controls [lung tumor fraction, median(95%CI), respectively: 15(9-23) and 33(26-39) % of lung volume; P<0.001]. In vitro Cre-mediated Creb1 deletion or treatment of CCLC with CREB-inhibitor ICG-001 diminished cellular proliferation, in vivo tumor growth, and spontaneous lung metastasis. KRAS silencing in CCLC lead to decreased CREB activation, whereas microarray analysis of Creb-1 deleted CCLC revealed marked reductions in C-X-C chemokine expression. CREB signaling is essential for KRAS-driven lung adenocarcinoma by augmenting tumor-associated inflammation.This work was supported by European Research Council Starting Independent Investigator (#260524) and Proof-of-Concept (#679345) Grants. ER -