delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles
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Date
2009-03-10
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Authors
Zeng, Yan
Abdallah, Agustin
Lu, Jian-Ping
Wang, Tao
Chen, Yan-Hua
Terrian, David M.
Kim, Kwonseop
Lu, Qun
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Publisher
East Carolina University
Abstract
Background: delta-Catenin is a unique member of delta-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, delta-catenin is upregulated in human prostatic adenocarcinomas, although the effects of delta-catenin overexpression in prostate cancer are unclear. We hypothesized that delta-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival.
Results: We employed gene transfection and small interfering RNA to demonstrate that increased delta-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. delta-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of delta-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival
regulation. delta-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, delta-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1.
Conclusion: Taken together, our studies suggest that at least one consequence of an increased expression of delta-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.
Originally published Molecular Cancer, Vol. 8, No. 19, Mar 2009
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Citation
Molecular Cancer; 8:19 p. 1-11
DOI
10.1186/1476-4598-8-19