Silencing of the GnRH type 1 receptor blocks the antiproliferative effect of the GnRH agonist, leuprolide, on the androgen-independent prostate cancer cell line DU145

Y. H. Ko, Y. R. Ha, J. W. Kim, Sung-Gu Kang, H. A. Jang, Seok Ho Kang, Hong Seok Park, Jun Cheon

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4 Citations (Scopus)

Abstract

This study investigated the mechanism of action of a gonadotropin-releasing hormone (GnRH) agonist, leuprolide, on proliferation of the hormone-refractory prostate cancer cell line DU145, transfected with short hairpin RNA (shRNA), to reduce expression of the GNRHR1 gene (which encodes the GnRH type 1 receptor). DU145 cell proliferation in the presence of leuprolide (10-9 and 10-7 M) or control medium was measured before and after GnRHR1 knockdown. Reverse transcription-polymerase chain reaction and Western blot analysis were used to measure the degree of GNRHR1 silencing. DU145 cells treated with leuprolide (10-9 and 10-7 M) showed significant growth inhibition compared with control-treated DU145 cells. Transfection with GNRHR1-shRNA significantly decreased GNRHR1 expression at 48 h. DU145 cells transfected with silencing GNRHR1-shRNA showed normal growth patterns; however, there was no significant inhibition of proliferation of DU145 cells transfected with GNRHR1-shRNA compared with cells transfected with control-shRNA in response to leuprolide. These data demonstrated that the antiproliferative effect of leuprolide was mediated by the GnRHR1.

Original languageEnglish
Pages (from-to)729-739
Number of pages11
JournalJournal of International Medical Research
Volume39
Issue number3
DOIs
Publication statusPublished - 2011 Jan 1

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Keywords

  • Cell proliferation
  • DU145 cells
  • GnRH type 1 receptor
  • Gonadotropin-releasing hormone (GnRH) agonist
  • Hormone therapy
  • Leuprolide
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

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