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

Matthias D. Hofer, Alice Fecko, Ronglai Shen, Sunita R. Setlur, Kenneth G. Pienta, Scott A. Tomlins, Arul M. Chinnaiyan, Mark A. Rubin*

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

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-β 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-β expression level. Protein expression of PDGFR-β, 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-β expression and divided tumors in groups based on PDGFR-β expression level. Performing a supervised analysis to identify potential comarkers of PDGFR-β in PCa, we identified a set of genes whose expression was associated with PDGFR-β status including early growth response 1 (Egr1), an upstream effector of PDGF (4.2-fold upregulation), α-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.

Original languageEnglish (US)
Pages (from-to)503-512
Number of pages10
JournalNeoplasia
Volume6
Issue number5
DOIs
StatePublished - Jan 1 2004

Keywords

  • Imatinib mesylate
  • Platelet-derived growth factor receptor (PDGFR)
  • Prostate cancer
  • Tissue microarray
  • cDNA expression

ASJC Scopus subject areas

  • Cancer Research

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    Hofer, M. D., Fecko, A., Shen, R., Setlur, S. R., Pienta, K. G., Tomlins, S. A., Chinnaiyan, A. M., & Rubin, M. A. (2004). Expression of the platelet-derived growth factor receptor in prostate cancer and treatment implications with tyrosine kinase inhibitors. Neoplasia, 6(5), 503-512. https://doi.org/10.1593/neo.04157