Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

Abstract

To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.

• Authors: Alfonso Calvo, Nianqing Xiao, Jason Kang, Carolyn J M Best, Isabel Leiva, Michael R Emmert-Buck, Cheryl Jorcyk, Jeffrey E Green
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 18 Pg. 5325-35 (Sep 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12235003 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cell Adhesion Molecules
• Proteins
• Selenoprotein P
• Selenoproteins

Topics

• Animals
• Cell Adhesion Molecules (biosynthesis, genetics)
• Cell Division (genetics, physiology)
• Cluster Analysis
• Disease Progression
• Down-Regulation
• Gene Expression Profiling
• Humans
• Male
• Mice
• Neoplasm Invasiveness
• Neovascularization, Pathologic (genetics, metabolism, pathology)
• Oligonucleotide Array Sequence Analysis
• Prostatic Neoplasms (blood supply, genetics, metabolism, pathology)
• Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Selenoprotein P
• Selenoproteins
• Tumor Cells, Cultured