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Journal of Biomedicine and Biotechnology
Volume 2005, Issue 4, Pages 353-363
http://dx.doi.org/10.1155/JBB.2005.353
Research article

Coherent Expression Chromosome Cluster Analysis Reveals Differential Regulatory Functions of Amino-Terminal and Distal Parathyroid Hormone-Related Protein Domains in Prostate Carcinoma

1Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093-0654, USA
2San Diego Supercomputer Center, University of California, San Diego, CA 92093-0505, USA
3Department of Medicine, University of California, San Diego, CA 92161-0813, USA
4Anesthesiology Service, VA San Diego Healthcare System, Department of Anesthesiology, University of California, San Diego, CA 92161-8770, USA
5Medicine Service, VA San Diego Healthcare System, Department of Medicine, University of California, San Diego, CA 92161-9111, USA

Received 14 February 2005; Revised 10 May 2005; Accepted 16 May 2005

Copyright © 2005 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Parathyroid hormone-related protein (PTHrP) has a number of cancer-related actions. While best known for causing hypercalcemia of malignancy, it also has effects on cancer cell growth, apoptosis, and angiogenesis. Studying the actions of PTHrP in human cancer is complicated because there are three isoforms and many derived peptides. Several peptides are biologically active at known or presumed cell surface receptors; in addition, the PTHrP-derived molecules can exert effects at the cell nucleus. To address this complexity, we studied gene expression in a DU 145 prostate cancer cell line that was stably transfected with control vector, PTHrP 1-173 and PTHrP 33-173. With this model, regulatory effects of the amino-terminal portion of PTHrP would result only from transduction with the full-length molecule, while effects pertaining to distal sequences would be evident with either construct. Analysis of the expression profiles by microarrays demonstrated nonoverlapping groups of differentially expressed genes. Amino-terminal PTHrP affected groups of genes involved in apoptosis, prostaglandin and sex steroid metabolism, cell-matrix interactions, and cell differentiation, while PTHrP 33-173 caused substantial increases in MHC class I antigen expression. This work demonstrates the distinct biological actions of the amino-terminus compared to distal mid-molecule or carboxy-terminal sequences of PTHrP in prostate carcinoma cells and provides targets for further study of the malignant process.