Additive Effect of Zfhx3/Atbf1 and Pten Deletion on Mouse Prostatic Tumorigenesis

作     者：Xiaodong Sun Changsheng Xing Xiaoying Fu Jie Li Baotong Zhang Henry F.Frierson Jr. Jin-Tang Dong 

作者机构：Winship Cancer InstituteDepartment of Hematology and Medical OncologyEmory University School of Medicine Department of PathologyTianjin University of Traditional Chinese Medicine Department of PathologyUniversity of Virginia Health System 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2015年第42卷第7期

页      面：373-382页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported in part by the grants from the National Cancer Institute(NCI)(No.R01CA121459) the National Institutes of Health(NIH) supported in part by the Integrated Cellular Imaging Shared Resource of Winship Cancer Institute of Emory University the NIH/NCI under award number P30CA138292 

主　　题：ZFHX3 ATBFI PTEN Prostate cancer mPIN 

摘      要：The phosphatase and tensin homolog （PTEN） and the zinc finger homeobox 3 （ZFHX3）/AT-motif binding factor 1 （ATBF1） genes have been established as tumor suppressor genes in prostate cancer by their frequent deletions and mutations in human prostate cancer and by the formation of mouse prostatic intraepithelial neoplasia （mPIN） or tumor by their deletions in mouse prostates. However, whether ZFHX3/ATBF1 deletion together with PTEN deletion facilitates prostatic tumorigenesis is unknown. In this study, we simultaneously deleted both genes in mouse prostatic epithelia and performed histological and molecular analyses. While deletion of one Pten allele alone caused low-grade （LG） mPIN as previously reported, concurrent deletion of Zfhx3/Atbfl promoted the progression to high-grade （HG） mPIN or early carcinoma. ZJhx3/Atbfl and Pten deletions together increased cell proliferation, disrupted the smooth muscle layer between epithelium and stroma, and increased the number of apoptotic cells. Deletion of both genes also accelerated the activation of Akt and Erkl/2 oncoproteins. These results suggest an additive effect of ZFHX3/ATBF1 and PTEN deletions on the development and progression of prostate neoplasia.