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: Xiaodong Sun, Changsheng Xing, Xiaoying Fu, Jie Li, Baotong Zhang, Henry F Frierson Jr, Jin-Tang Dong
• Journal: Journal of genetics and genomics = Yi chuan xue bao (J Genet Genomics) Vol. 42 Issue 7 Pg. 373-82 (Jul 20 2015) ISSN: 1673-8527 [Print] China
• PMID: 26233892 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Homeodomain Proteins
• Zfhx3 protein, mouse
• PTEN Phosphohydrolase

Topics

• Animals
• Gene Expression Regulation, Neoplastic (genetics, physiology)
• Homeodomain Proteins (genetics, metabolism)
• Male
• Mice
• PTEN Phosphohydrolase (genetics, metabolism)
• Prostatic Intraepithelial Neoplasia (genetics, metabolism, pathology)
• Prostatic Neoplasms (genetics, metabolism, pathology)