title: Cyclic AMP response element-binding protein overexpression: a feature associated with negative prognosis in never smokers with non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer deaths worldwide. Recent advances in targeted therapies hold promise for the development of new treatments for certain subsets of cancer patients by targeting specific signaling molecule. Based on the identification of the transcription factor cyclic AMP response element-binding protein (CREB) as an important regulator of growth of several types of cancers and our recent findings of its importance in normal differentiation of bronchial epithelial cells, we hypothesized that CREB plays an important pathobiologic role in lung carcinogenesis. We conducted this initial study to determine whether the expression and activation status of CREB are altered in non-small cell lung cancer (NSCLC) and of any prognostic importance in NSCLC patients. We found that the expression levels of mRNA and protein of CREB and phosphorylated CREB (p-CREB) were significantly higher in most of the NSCLC cell lines and tumor specimens than in the normal human tracheobronchial epithelial cells and adjacent normal lung tissue, respectively. Analysis of CREB mRNA expression and the CREB gene copy number showed that CREB overexpression occurred mainly at the transcriptional level. Immunohistochemical analysis of tissue microarray slides containing sections of NSCLC specimens obtained from 310 patients showed that a decreased survival duration was significantly associated with overexpression of CREB or p-CREB in never smokers but not in current or former smokers with NSCLC. These are the first reported results illustrating the potential of CREB as a molecular target for the prevention and treatment of NSCLC, especially in never smokers.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 USA.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Seo
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Katherine
authors.initials: K
authors.lastname: Pisters
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Ja Seok
authors.initials: JS
authors.lastname: Koo
mesh_terms: D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012907:Smoking / Q000235:genetics; D016019:Survival Analysis
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D012333:RNA, Messenger