Research

Candidate metastasis suppressor genes uncovered by array comparative genomic hybridization in a mouse allograft model of prostate cancer

Yajun Yi¹ , Srinivas Nandana² , Thomas Case² , Colleen Nelson³ , Tatjana Radmilovic¹ , Robert J Matusik² and Karen D Tsuchiya^4,5

¹  Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

²  Department of Urologic Surgery and Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

³  Department of Urologic Sciences, University of British Columbia, The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada

⁴  Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Laboratories, Seattle Children's Hospital, WA, USA

⁵  Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA, USA

author email corresponding author email

Molecular Cytogenetics 2009, 2:18doi:10.1186/1755-8166-2-18

Published:	26 September 2009

Abstract

Background

The purpose of this study was to identify candidate metastasis suppressor genes from a mouse allograft model of prostate cancer (NE-10). This allograft model originally developed metastases by twelve weeks after implantation in male athymic nude mice, but lost the ability to metastasize after a number of in vivo passages. We performed high resolution array comparative genomic hybridization on the metastasizing and non-metastasizing allografts to identify chromosome imbalances that differed between the two groups of tumors.

Results

This analysis uncovered a deletion on chromosome 2 that differed between the metastasizing and non-metastasizing tumors. Bioinformatics filters were employed to mine this region of the genome for candidate metastasis suppressor genes. Of the 146 known genes that reside within the region of interest on mouse chromosome 2, four candidate metastasis suppressor genes (Slc27a2, Mall, Snrpb, and Rassf2) were identified. Quantitative expression analysis confirmed decreased expression of these genes in the metastasizing compared to non-metastasizing tumors.

Conclusion

This study presents combined genomics and bioinformatics approaches for identifying potential metastasis suppressor genes. The genes identified here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human prostate cancer.