Title | Expression of the platelet-derived growth factor receptor in prostate cancer and treatment implications with tyrosine kinase inhibitors. |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Hofer MD, Fecko A, Shen R, Setlur SR, Pienta KG, Tomlins SA, Chinnaiyan AM, Rubin MA |
Journal | Neoplasia |
Volume | 6 |
Issue | 5 |
Pagination | 503-12 |
Date Published | 2004 Sep-Oct |
ISSN | 1522-8002 |
Keywords | Antineoplastic Agents, Benzamides, Cell Line, Tumor, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Oligonucleotide Array Sequence Analysis, Phosphorylation, Piperazines, Platelet-Derived Growth Factor, Prostatic Neoplasms, Protein Kinase Inhibitors, Pyrimidines, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Up-Regulation |
Abstract | The platelet-derived growth factor receptor (PDGFR) is a receptor tyrosine kinase overexpressed in a subset of solid tumors and therefore is the target of drugs inhibiting this function such as imatinib mesylate (Gleevec). Thus far, drug therapy has played a limited role in the treatment of localized prostate cancer (PCa). This study characterizes PDGFR-beta expression in a wide spectrum of PCa samples to provide empirical data as part of a rational treatment strategy. A survey of five published prostate expression array studies, including 100 clinically localized PCa, did not identify tumors with increased PDGFR-beta expression level. Protein expression of PDGFR-beta, as determined by immunohistochemistry, revealed 5% of clinically localized PCa and 16% of metastatic PCa cases to show moderate or strong expression. To develop a strategy to detect patients most likely to profit from Gleevec treatment, we analyzed cDNA expression array data from 10,000 transcripts for PDGFR-beta expression and divided tumors in groups based on PDGFR-beta expression level. Performing a supervised analysis to identify potential comarkers of PDGFR-beta in PCa, we identified a set of genes whose expression was associated with PDGFR-beta status including early growth response 1 (Egr1), an upstream effector of PDGF (4.2-fold upregulation), alpha-methylacyl-CoA racemase, as well as v-Maf and neuroblastoma suppressor of tumorigenicity (both with a 2.2-fold downregulation). Taken together, this study suggests that only a small subset of PCas may be amenable to tyrosine kinase inhibitors specific for PDGFR. |
DOI | 10.1593/neo.04157 |
Alternate Journal | Neoplasia |
PubMed ID | 15548358 |
PubMed Central ID | PMC1531653 |
Grant List | CA 97063 / CA / NCI NIH HHS / United States P50CA69568 / CA / NCI NIH HHS / United States P50CA90381 / CA / NCI NIH HHS / United States |