Upregulation Of Rab, A Member Of The Ras Gene Family, Is Associated With Accelerated Lung Tumor Progression In Mice Exposed In Utero To Secondhand Smoke

Rationale: While second-hand smoke (SHS) exposure is responsible for more than 7,000 lung cancer deaths annually among US nonsmokers, it is unclear whether there is an association between in utero SHS and lung cancer. We have reported that lungs of mice exposed in utero to SHS and as adults to ovalbumin exhibited up-regulation of miR-155-5p, miR-21-3p and miR-18a-5p and down-regulation of 16 tumor suppressor genes, all predicted targets of these 3 miRNAs, which have been characterized as oncogenic miRNAs. In this pilot study, we investigated whether in utero SHS exposure promotes an oncogenic milieu in lungs of adult mice. Methods: Pregnant Balb/c mice were exposed from gestational days 6 - 19 to 10 mg/m3 of SHS or filtered air. From 16-19 weeks of age, male offspring were treated with 4 weekly intraperitoneal injections of urethane (1 g/kg) or saline. At 44 weeks of age, mice were sacrificed. Broncho-alveolar lavage fluids (BALF) were collected for assessment of inflammatory responses and oxidative stress. Tumors were analyzed for number, size, volume, and histopathological classification. Lung RNA sequencing was also performed. Results: In utero SHS-adult urethane (SU) treatment significantly (p Citation Format: Alexandra Noel, Rui Xiao, Zakia Perveen, Viviana Le Donne, Daniel B. Paulsen, Arthur L. Penn. Upregulation of Rab, a member of the Ras gene family, is associated with accelerated lung tumor progression in mice exposed in utero to secondhand smoke. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-037.