title: Additive Effect of Zfhx3/Atbf1 and Pten Deletion on Mouse Prostatic Tumorigenesis.
abstract: 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/Atbf1 promoted the progression to high-grade (HG) mPIN or early carcinoma. Zfhx3/Atbf1 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 Erk1/2 oncoproteins. These results suggest an additive effect of ZFHX3/ATBF1 and PTEN deletions on the development and progression of prostate neoplasia.
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Xing
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA; Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA.
authors.forename: Baotong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Virginia Health System, Charlottesville 22908, USA.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Frierson
authors.affiliation: Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, USA. Electronic address: j.dong@emory.edu.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018398:Homeodomain Proteins; C489511:Zfhx3 protein, mouse; D051059:PTEN Phosphohydrolase
keywords: ATBF1; PTEN; Prostate cancer; ZFHX3; mPIN