Cigarette Smoke upregulates Notch1 signaling pathway in lung adenocarcinoma

Notch-1 pathway plays an important role in lung carcinoma in the stem cell regulation, cellular communication, growth and differentiation. Cigarette smoke has an important role in Notch signaling activation in lung cancer. However, current data regarding the impact of cigarette smoke on the Notch pathway in lung cancer progression are limited. The present study was aimed at exploring whether cigarette smoke exposure altered the expression of Notch1 pathway by ex-vivo (surgical samples of lung parenchyma from smoker and non smoker patients with lung adenocarcinoma) and in vitro (adenocarcinoma A549 cell line) approaches. The expression of Notch1 and its ligand Jagged-1 in surgical samples was evaluated by immunohistochemistry. For the in vitro study, A549 were exposed to cigarette smoke extracts (CSE 2.5% and 5% for 6, 24 and 48 h) and the expression of Notch1, Jagged-1 and Hes-1 was evaluated by Real Time PCR and Western Blot (nuclear and cytoplasmic fractions). Expression and localization of Hes1 was also assessed by confocal microscopy. Higher expression of Notch-1 and Jagged-1 were observed in Smokers compared with non-Smokers. In A549, CSE exposure increased Notch-1, Jagged-1 and Hes-1 mRNA and protein levels. Confocal microscopy further confirmed higher expression of Hes-1 in the nuclei of cigarette smoke stimulated A549 cells. In conclusion, these data show that cigarette smoke may promote the activation of Notch1 pathway, corroborating its role as future hallmark of lung cancer progression and as a new target for lung cancer treatment.