Amplification of the urokinase gene and the sensitivity of prostate cancer cells to urokinase inhibitors

Merja A. Helenius, Kimmo J. Savinainen, G. Steven Bova, Tapio Visakorpi

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: To evaluate the frequency of the urokinase-type plasminogen activator (uPA) gene amplification and the sensitivity of prostate cancer cells to uPA inhibition, as we previously found one hormone-refractory prostate tumour with high-level amplification of the uPA (alias PLAU) gene, and also showed that a uPA inhibitor, amiloride, can effectively reduce the invasion potential of the PC-3 prostate cancer cell line. MATERIALS AND METHODS: Sixty-three locally recurrent hormone-refractory tumours and 78 hormone-refractory metastases from 29 patients who died from prostate cancer were analysed for uPA gene-copy number using fluorescence in situ hybridization. The Matrigel invasion assay was used to study the influence of uPA inhibitors on the invasive potential of prostate cancer cell lines. RESULTS: Of the locally recurrent hormone-refractory tumours, 21% had an increased copy number of uPA, but no high-level amplifications were found; 31% of the metastases had increased copy number and one high-level amplification of the uPA. Matrigel invasion assays with two specific uPA inhibitors, B428 and p-aminobenzamidine, showed that invasion of a prostate cancer cell line containing uPA gene amplification was inhibited by these small-molecule uPA inhibitors, while invasion of prostate cell lines without uPA gene amplification were not. CONCLUSION: These results suggest that selective inhibition of the uPA pathway in individuals whose tumours contain uPA gene amplification may provide therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)404-409
Number of pages6
JournalBJU International
Volume97
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Gene amplification
  • PLAU
  • Prostate cancer
  • Urokinase

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'Amplification of the urokinase gene and the sensitivity of prostate cancer cells to urokinase inhibitors'. Together they form a unique fingerprint.

Cite this