BioMed Research International

BioMed Research International / 2005 / Article

Research article | Open Access

Volume 2005 |Article ID 720954 | https://doi.org/10.1155/JBB.2005.353

I. Tsigelny, D. W. Burton, Y. Sharikov, R. H. Hastings, L. J. Deftos, "Coherent Expression Chromosome Cluster Analysis Reveals Differential Regulatory Functions of Amino-Terminal and Distal Parathyroid Hormone-Related Protein Domains in Prostate Carcinoma", BioMed Research International, vol. 2005, Article ID 720954, 11 pages, 2005. https://doi.org/10.1155/JBB.2005.353

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

Received14 Feb 2005
Revised10 May 2005
Accepted16 May 2005

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.

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.


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