Expression of the platelet-derived growth factor receptor in prostate cancer and treatment implications with tyrosine kinase inhibitors.

TitleExpression of the platelet-derived growth factor receptor in prostate cancer and treatment implications with tyrosine kinase inhibitors.
Publication TypeJournal Article
Year of Publication2004
AuthorsHofer MD, Fecko A, Shen R, Setlur SR, Pienta KG, Tomlins SA, Chinnaiyan AM, Rubin MA
Date Published2004 Sep-Oct
KeywordsAntineoplastic 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

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.

Alternate JournalNeoplasia
PubMed ID15548358
PubMed Central IDPMC1531653
Grant ListCA 97063 / CA / NCI NIH HHS / United States
P50CA69568 / CA / NCI NIH HHS / United States
P50CA90381 / CA / NCI NIH HHS / United States