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Originally published In Press as doi:10.1074/mcp.M700190-MCP200 on November 8, 2007.
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Molecular & Cellular Proteomics 7:411-423, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.


Research

Monitoring Mouse Prostate Development by Profiling and Imaging Mass Spectrometry*,S

Pierre Chaurand{ddagger}, Mohammad A. Rahman§, Tamela Hunt§, James A. Mobley, Guangyu Gu§, Joey C. Latham{ddagger}, Richard M. Caprioli{ddagger} and Susan Kasper§,||

From the {ddagger} Mass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232-8575, § Department of Urologic Surgery, Vanderbilt University, Nashville, Tennessee 37232-2765, and Department of Surgery, Division of Urology, University of Alabama, Birmingham, Alabama 35233

Mass spectrometry-based tissue profiling and imaging are technologies that allow identification and visualization of protein signals directly on thin sections cut from fresh frozen tissue specimens. These technologies were utilized to evaluate protein expression profiles in the normal mouse prostate during development (1–5 weeks of age), at sexual maturation (6 weeks of age), and in adult prostate (at 10, 15, or 40 weeks of age). The evolution of protein expression during normal prostate development and maturation were subsequently compared with 15-week prostate tumors derived from genetically engineered mice carrying the Large T antigen gene under regulation of the prostate-specific probasin promoter (LPB-Tag mouse model for prostate cancer). This approach identified proteins differentially expressed at specific time points during prostate development. Furthermore expression of some of these proteins, for example probasin and spermine-binding protein, were associated with prostate maturation, and prostate tumor formation resulted in their loss of expression. Cyclophilin A, a protein found in other cancers, was differentially {alpha}-acetylated on the N terminus, and both isoforms appeared during normal prostate and prostate tumor development. Imaging mass spectrometry localized the protein signals to specific prostatic lobes or regions. Thus, tissue profiling and imaging can be utilized to analyze the ontogeny of protein expression during prostate morphogenesis and tumorigenesis and identify proteins that could potentially serve as biomarkers for prostate cancer.


|| To whom correspondence should be addressed: Dept. of Urologic Surgery, A-1302 MCN, Vanderbilt University, Nashville, TN 37232-2765. Tel.: 615-343-5921; Fax: 615-322-8990; E-mail: susan.kasper{at}vanderbilt.edu


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