δ-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles
1 Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
2 Leo Jenkins Cancer Center, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
3 Department of Surgery, Beijing Capital Medical University, Beijing, PR China
4 College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea
Molecular Cancer 2009, 8:19 doi:10.1186/1476-4598-8-19Published: 10 March 2009
δ-Catenin is a unique member of β-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, δ-catenin is upregulated in human prostatic adenocarcinomas, although the effects of δ-catenin overexpression in prostate cancer are unclear. We hypothesized that δ-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival.
We employed gene transfection and small interfering RNA to demonstrate that increased δ-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. δ-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 δ-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. δ-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, δ-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1.
Taken together, our studies suggest that at least one consequence of an increased expression of δ-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.