Abstract 932: The impact of e-cigarette exposure on pulmonary epithelium gene expression and transformation (2014)

Abstract Lung cancer is the leading cause of cancer-related mortality in the United States. Despite a strong correlation between cigarette smoking and the onset of lung cancer, the prevalence of smoking still remains high. The electronic cigarette (ECIG) is designed to deliver nicotine without combusting tobacco. Since nicotine is widely considered the addictive component in tobacco with limited ability to initiate cancer, ECIGs have been advertised to be a safer alternative to tobacco cigarettes (TCIGs). However, the potential health risks and carcinogenicity of ECIGs have not previously been evaluated. In this study, we assess the impact of in vitro ECIG exposure on the carcinogenic potential of immortalized human bronchial epithelial cells on a background of silenced p53 and activated KRAS (H-P53/KRAS). This model is utilized because p53 and KRAS mutations are often observed in the airway of current and former smokers at risk for lung cancer. Our preliminary results suggest that ECIG-induced alterations may be dependent upon the mutational landscape of the airway cells being exposed. In anchorage independent growth assays, the in vitro correlate of malignant transformation, we found enhanced colony growth in the H-P53/KRAS cells following a 10-day treatment with the high nicotine ECIG-conditioned media compared to the untreated and low nicotine treatment groups. We next assessed the effect of ECIG exposure on cell invasion using three-dimensional air-liquid interface (ALI) models. H-P53KRAS cells exhibited invasion-associated morphological changes following a 10-day treatment with the high nicotine conditioned media, including increased proliferation, diminished cell-cell cohesion and the appearance of cells percolating out of and breaching the modified basement membrane. Finally, gene expression profiles show 263 differentially expressed genes following exposure to high nicotine ECIG-conditioned media for 96hrs. The ECIG-conditioned media induced a gene expression pattern similar to TCIG-conditioned media and whole cigarette smoke exposure in the H-P53/KRAS cells. We will next compare the ECIG-induced gene expression signature to carcinogenicity-related gene signatures established in previous and ongoing clinical investigations and test ECIG-altered candidate genes for their ability to drive the malignant transformation of airway epithelial cells. These studies will determine the impact of ECIG exposure on lung carcinogenicity and provide needed scientific guidance to the FDA regarding the physiologic effects of ECIGs. These studies were supported by funding from the following: NIH/NCI #U01CA152751 (SMD, TCW), NCI #U01CA152751-S1 (SMD, TCW, SJP), NCI #U01CA152751-AS (SMD, KK), NCI #T32-CA009120-36 (SMD, SJP, PCP), NIH/NHLBI #T32HL072752 (SMD, EL), University of California Tobacco-Related Disease Research Program (TRDRP) #18FT-0060 (TCW), TRDRP #20KT-0055 (TCW), Lung Cancer SPORE (P50CA70907, JDM, JEL) Citation Format: Stacy J. Park, Tonya C. Walser, Catalina Perdomo, Teresa Wang, Long-Sheng Hong, Paul C. Pagano, Elvira L. Liclican, Kostyantyn Krysan, Jill E. Larsen, Michael C. Fishbein, John D. Minna, Marc E. Lenburg, Avrum Spira, Steven M. Dubinett. The impact of e-cigarette exposure on pulmonary epithelium gene expression and transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 932. doi:10.1158/1538-7445.AM2014-932