Expression of the Platelet-Derived Growth Factor Receptor in Prostate Cancer and Treatment Implications with Tyrosine Kinase Inhibitors
| Autor: | Matthias D. Hofer, Alice Fecko, Ronglai Shen, Sunita R. Setlur, Kenneth G. Pienta, Scott A. Tomlins, Arul M. Chinnaiyan, Mark A. Rubin |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 6, Iss 5, Pp 503-512 (2004) |
| Druh dokumentu: | article |
| ISSN: | 1476-5586 1522-8002 |
| DOI: | 10.1593/neo.04157 |
| Popis: | 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 (Egri), 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. |
| Databáze: | Directory of Open Access Journals |
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