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Author Notes:
Correspondence to: Jin-Tang Dong, Telephone: +1 404 712 2568. fax: +1 404 778 5530. ; Email: j.dong@emory.edu (J.-T. Dong).
Subjects:
Research Funding:
This work was supported in part by grant R01CA121459 from the National Cancer Institute, National Institutes of Health.
It was also supported in part by the Integrated Cellular Imaging Shared Resource of Winship Cancer Institute of Emory University and the NIH/NCI under award number P30CA138292.
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Biochemistry & Molecular Biology
- Genetics & Heredity
- ZFHX3
- ATBF1
- PTEN
- Prostate cancer
- mPIN
- SUPPRESSOR GENE LEADS
- TUMOR SUPPRESSION
- SIGNALING PATHWAYS
- CANCER GENOMICS
- BREAST-CANCER
- MODEL
- MICE
- PROGRESSION
- NKX3.1
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.
Copyright information:
© 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China.
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
