Faculty Collaboration Database

Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium. BMC Genomics 2004 Aug 20;5(1):58

Date

08/21/2004

Pubmed ID

15318950

Pubmed Central ID

PMC516028

DOI

10.1186/1471-2164-5-58

Scopus ID

2-s2.0-9144233084 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

BACKGROUND: Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations.

RESULTS: Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using tissue microarrays to demonstrate a significant association between downregulated protein expression and tumorigenesis, a process that is the reverse of what is seen in the presence of Selenium.

CONCLUSIONS: Thus the outlined process demonstrates similar baseline and selenium induced gene expression profiles between rat and human prostate cancers, and provides a method for identifying testable functional pathways for the action of Selenium's chemopreventive properties in prostate cancer.

Author List

Schlicht M, Matysiak B, Brodzeller T, Wen X, Liu H, Zhou G, Dhir R, Hessner MJ, Tonellato P, Suckow M, Pollard M, Datta MW

Author

Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
Anticarcinogenic Agents
Cell Line, Tumor
DNA, Neoplasm
Expressed Sequence Tags
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Insulin-Like Growth Factor Binding Protein 3
Male
Neoplasm Proteins
Prostatic Neoplasms
RNA, Messenger
RNA, Neoplasm
Rats
Retinoid X Receptor alpha
Selenium
Selenomethionine
Species Specificity
Subtraction Technique