Primary research

INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling

Stephanie Filleur^1,2 , Jennifer Hirsch¹ , Aline Wille³ , Margarete Schön⁴ , Christian Sell⁵ , Michael H Shearer² , Thomas Nelius¹ and Ilse Wieland³

¹  Texas Tech University Health Sciences Center, Department of Urology, Lubbock, TX, USA

²  Texas Tech University Health Sciences Center, Department of Microbiology and Immunology, Lubbock, TX, USA

³  Institute for Human Genetics, Otto-von-Guericke University, Magdeburg, Germany

⁴  Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine and Department of Dermatology, University of Würzburg, Würzburg, Germany

⁵  Department of Pathology, Drexel University College of Medicine, Philadelphia, PA, USA

author email corresponding author email

Cancer Cell International 2009, 9:28doi:10.1186/1475-2867-9-28

Published:	11 November 2009

Abstract

Background

The gene encoding integrator complex subunit 6 (INTS6), previously known as deleted in cancer cells 1 (DICE1, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest INTS6/DICE1 as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of INTS6/DICE1 on prostate cancer cells.

Results

Markedly decreased INTS6/DICE1 mRNA levels were detected in prostate cancer cell lines LNCaP, DU145 and PC3 as well as CPTX1532 as compared to a cell line derived from normal prostate tissue, NPTX1532. Exogenous re-expression of INTS6/DICE1 cDNA in androgen-independent PC3 and DU145 cell lines substantially suppressed their ability to form colonies in vitro. This growth inhibition was not due to immediate induction of apoptosis. Rather, prostate cancer cells arrested in G1 phase of the cell cycle. Expression profiling of members of the Wnt signaling pathway revealed up-regulation of several genes including disheveled inhibitor CXXC finger 4 (CXXC4), frizzled homologue 7 (FZD7), transcription factor 7-like 1 (TCF7L1), and down-regulation of cyclin D1.

Conclusion

These results show for the first time a link between INTS6/DICE1 function, cell cycle regulation and cell-cell communication involving members of the Wnt signaling pathway.