Abstract 257: R4 knock-out mice showed lung hyperplasia and susceptible to urethane-induced lung carcinogenesis

Abstract

Abstract Lung cancer is responsible for 1.3 million deaths worldwide annually. There have been several reports on candidate genes driving lung cancers including ras. However still it is needed to find new genes which can cause lung cancers. Recently we developed R4 knock-out (KO) mice which showed larger relative lung weight and volume than age-matched wild-type (WT) mice. Lung hyperplasia was found with increased alveolar thickness in 6, 18 and 40 week-old R4 KO mice. Also, this finding was observed in E16.5 and 18.5 day KO mice. Cell cycle markers including PCNA and cyclinD1 were highly expressed in the lung of R4 KO mice than WT mice. PCNA positive cells were mostly type 2 pneumocytes. To determine the susceptibility of lung cancer in R4 KO mice, we induced lung cancer by the injection of 1g/kg urethane weekly for a total of eight doses. Twenty weeks after the initial injection, mice were sacrificed, and the lungs were fixed, and the number of tumors on the lung surface was assessed. Also lung tumors were scanned by micro-CT at the end of the lung carcinogenesis protocol for measure the tumor diameter. Surface lung tumor number is significantly increased in KO mice. And tumor size is also significantly larger in KO mice than WT. Histological findings showed more severe well differentiated lung adenoma in urethane-injected R4 KO mice. We conclude that R4 KO mice is susceptible to tumorigenesis in the urethane model and the functional loss of R4 gene may cause lung cancer. Therefore, R4 gene has a possibility as a potential target for chemoprevention of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 257.