Overexpressed Raf-1 and phosphorylated cyclic adenosine 3'-5'-monophosphatate response element-binding protein are early markers for lung adenocarcinoma.

Background: Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer and has a high mortality. The tobacco carcinogen nicotine-derived nitrosamine 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) stimulates the proliferation of human PAC cells and small airway epithelial cells through beta-1 adrenorecptor-mediated transactivation of the epidermal growth factor receptor (EGFR).

Methods: Using the NNK hamster PAC model and human PAC tissue arrays with matched and unmatched normal lung tissues, the authors tested the hypothesis that Raf-1, an effector of the EGFR, and P-CREB, an effector of the beta-adrenoreceptor, are overexpressed in a significant subset of human PACs and are early markers of PAC development.