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J. Biol. Chem., Vol. 280, Issue 43, 36442-36451, October 28, 2005
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1
From the
Departments of
Cancer Biology and
Pathology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157 and ¶Department of Molecular and Medical Pharmacology, University of California Los Angeles School of Medicine, Los Angeles, California 90095
Genetically engineered mice are being used increasingly for delineating the molecular mechanisms of prostate cancer development. Epithelium-stroma interactions play a critical role in prostate development and tumorigenesis. To better understand gene expression patterns in the normal sexually mature mouse prostate, epithelium and stroma were laser-capture microdissected from ventral, dorsolateral, and anterior prostate lobes. Genome-wide expression was measured by DNA microarrays. Our analysis indicated that the gene expression pattern in the mouse dorsolateral lobe was closest to that of the human prostate peripheral zone, supporting the hypothesis that these prostate compartments are functionally equivalent. Stroma from a given lobe had closer gene expression patterns with stroma from other lobes than epithelium from the same lobe. Stroma appeared to have higher expression complexity than epithelium. Specifically, stromal cells had higher expression levels of genes implicated in cell adhesion, muscle development, and contraction, in structural constituents of cytoskeleton and actin binding, and in components such as sarcomere and extracellular matrix collagen. Among the genes that were enriched in the epithelium were secretory proteins, including seminal vesicle protein secretion 2 and 5. Surprisingly, prostate stroma expressed many osteogenic molecules, as confirmed by immunohistochemistry. A "bone-like" environment in the prostate may predispose prostate cells for survival in the bone. Chemokine Cxcl12 but not its receptor, Cxcr4, was expressed in normal prostate. In prostate tumors, interestingly, Cxcl12 was up-regulated in epithelial cells with a concomitant expression of Cxcr4. Expression of both the receptor and ligand may provide an autocrine mechanism for tumor cell migration and invasion.
Received for publication, May 4, 2005 , and in revised form, July 11, 2005.
* This work was supported by National Institutes of Health Grants R01ES11124 and R01CA107668. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables I and II.
1 To whom correspondence should be addressed: Dept. of Cancer Biology, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157. Tel.: 336-713-7655; Fax: 336-713-7660; E-mail: yqchen{at}wfubmc.edu.
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