Prostate cancer has a complex pathogenesis in which many men develop early stage 'benign' cancers, and a much smaller but substantial number develop aggressive cancers that metastasize and cause premature death. The PI has identified a region on chromosome 13q21 which appears to contain a gene whose alteration contributes to the aggressive behavior of prostate cancer. This region is subject to LOH and homozygous deletion in aggressive prostate cancers and cell lines. The current minimal region contains at least three genes which are expressed in normal prostate and low-grade tumors, but not aggressive cancers. The PI now proposes to define the smallest region of deletions that contains the 13q21 gene; to identify the 13q21 tumor suppressor gene (TSG) through expression and mutation analyses; to express the gene in cancer cell lines to examine effects on growth and metastasis; and examine in greater detail how often LOH and homozygous deletion affect the gene, the expression of the gene in prostate cancer, and clinical and pathologic correlations including prognostic significance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA087921-02
Application #
6378108
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Okano, Paul
Project Start
2000-08-18
Project End
2002-03-31
Budget Start
2001-08-01
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$232,200
Indirect Cost
Name
University of Virginia
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Ci, Xinpei; Xing, Changsheng; Zhang, Baotong et al. (2015) KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1? accumulation. Mol Cancer 14:91
Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong et al. (2014) Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways. Neoplasia 16:883-99
Xing, Changsheng; Fu, Xiaoying; Sun, Xiaodong et al. (2013) Lack of an additive effect between the deletions of Klf5 and Nkx3-1 in mouse prostatic tumorigenesis. J Genet Genomics 40:315-8
Xing, Changsheng; Fu, Xiaoying; Sun, Xiaodong et al. (2013) Different expression patterns and functions of acetylated and unacetylated Klf5 in the proliferation and differentiation of prostatic epithelial cells. PLoS One 8:e65538
Zhao, Ke-Wen; Sikriwal, Deepa; Dong, Xueyuan et al. (2011) Oestrogen causes degradation of KLF5 by inducing the E3 ubiquitin ligase EFP in ER-positive breast cancer cells. Biochem J 437:323-33
Guo, Peng; Dong, Xue-Yuan; Zhao, Ke-Wen et al. (2010) Estrogen-induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER-positive breast cancer cells. Int J Cancer 126:81-9
Guo, Peng; Zhao, Ke-Wen; Dong, Xue-Yuan et al. (2009) Acetylation of KLF5 alters the assembly of p15 transcription factors in transforming growth factor-beta-mediated induction in epithelial cells. J Biol Chem 284:18184-93
Guo, Peng; Dong, Xue-Yuan; Zhang, Xiaohui et al. (2009) Pro-proliferative factor KLF5 becomes anti-proliferative in epithelial homeostasis upon signaling-mediated modification. J Biol Chem 284:6071-8
Chen, C; Sun, X; Guo, P et al. (2007) Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. Oncogene 26:2386-94
Chen, Ceshi; Zhou, Zhongmei; Ross, Jeffrey S et al. (2007) The amplified WWP1 gene is a potential molecular target in breast cancer. Int J Cancer 121:80-87

Showing the most recent 10 out of 21 publications