delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles.
BACKGROUND
delta-Catenin is a unique member of beta-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.


CONCLUSIONS
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.
Zeng
Yan
Y
Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA. zy717@yeah.net
Abdallah
Agustin
A
Lu
Jian-Ping
JP
Wang
Tao
T
Chen
Yan-Hua
YH
Terrian
David M
DM
Kim
Kwonseop
K
Lu
Qun
Q
D000818:Animals; D051186:Armadillo Domain Proteins / Q000737:chemistry / Q000378:metabolism; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D017434:Protein Structure, Tertiary; D023041:Xenograft Model Antitumor Assays; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D000095002:Delta Catenin