MP71-17 FLCN KNOCKOUT MICE DEVELOP LUNG TUMORS AND OTHER NEOPLASIA IN MULTIPLE ORGANS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2016MP71-17 FLCN KNOCKOUT MICE DEVELOP LUNG TUMORS AND OTHER NEOPLASIA IN MULTIPLE ORGANS Jindong Chen, Sue Schoen, Guang-Qian Xiao, Bin Tean Teh, and Guan Wu Jindong ChenJindong Chen More articles by this author , Sue SchoenSue Schoen More articles by this author , Guang-Qian XiaoGuang-Qian Xiao More articles by this author , Bin Tean TehBin Tean Teh More articles by this author , and Guan WuGuan Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1463AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES FLCN was originally identified in patients with Birt–Hogg–Dube' (BHD) disease which is a hereditary cancer syndrome characterized by development of lesions/tumors in multiple organs including skin, kidney, lung. We have previously created kidney-specific FLCN knockout mouse models that develop kidney cysts and malignant renal tumors. To determine whether FLCN mutations cause tumors in other organs, we herein developed a conditional FLCN whole-body knockout mouse models through LoxP-CMV-Cre system. METHODS FLCN-floxed mice were crossed to CMV-Cre transgenic mice to produce FLCN-CMV-Cre knockout mice. All mice were manipulated and housed in full compliance with applicable regulations. Genotyping was carried out by PCR. Totally 64 FLCN+/-/CMV-Cre heterozygous mice and 56 normal control littermates were collected for phenotyping and histopathological analysis. Mouse body weight, kidney weight were measured upon euthanasia by CO2 inhalation. Tissues including kidneys, lung, liver, spleen, heart, stomach, intestine, brain, testes were collected and fixed and paraffin embedded following the routine protocol. Paraffin blocks were sectioned at 3 µm thick and stained with hematoxylin and eosin (H&E). Stained slides were evaluated by a board-certified pathologist. Immunohistochemical analysis was performed following the manufactory’s protocols. Routine Western blot assay was adopted for protein expression analysis. RESULTS While FLCN null mice is embryonic lethal, FLCN heterozygous mice (FLCN+/-/CMV-Cre) develop lung cancer, kidney tumor, renal cyst, and other types of neoplasm. Of 45 observed tumors, 19 (42.2% ) were papillary lung cancers, 10 (22.2%) were kidney tumors, 5 (11.1%) were ovarian tumors, 3 (6.7%) were cervical tumors, 2 (4.4%) gastric tumors, 2 were (4.4%) liver cancers, 2 (4.4%) were skin tumors, 1 (2.2%) was lymphoma, and 1 (2.2%) sarcoma. In addition, 38 kidney cysts were observed. In contrast, we only observed one lung cancer case in 56 normal control mice. CONCLUSIONS These results suggest that FLCN is a critical universal tumor suppressor and its mutations could lead to tumorigenesis in multiple organs. This mouse model provides a useful tool for studying the multi-function of FLCN in the related organs, and further investigations will provide insights into the pathogenesis of the FLCN-associated tumors. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e922 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jindong Chen More articles by this author Sue Schoen More articles by this author Guang-Qian Xiao More articles by this author Bin Tean Teh More articles by this author Guan Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...