Endothelin-1 production by prostate cancer cell lines is up-regulated by factors involved in cancer progression and down-regulated by androgens

Simone Granchi, Sandro Brocchi, Lorella Bonaccorsi, Elisabetta Baldi, Maria Cristina Vinci, Gianni Forti, Mario Serio, Mario Maggi

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Recent data demonstrate that endothelin-1 (ET-1) concentration increases in plasma of men with advanced, hormone-refractory prostate adenocarcinoma. In addition, ET-1 is involved in osteblastic remodelling and new bone formation, suggesting a role for this vasoactive peptide in the metastatic progression of prostate cancer to the bone. METHODS. We investigated the regulation of ET-1 expression in androgen-sensitive and insensitive prostate cancer cell lines by androgens and several factors involved in progression of prostate cancer (EGF) and bone remodelling (TGFβ-1, IL1-α and IGF-1). RESULTS. Northern analysis and radio immunoassay demonstrated that all the ET-1 pathways are tuned off in the androgen-sensitive LNCaP cell line when compared to the androgen-insensitive PC-3 and DU145. In PC-3 cells transfected with a full-length androgen receptor expression vector (PC-3-AR), treatment with androgens reduced gene expression and secretion of ET-1 without affecting the gene expression of ET-3. Collectively, these data support a role for androgens in the regulation of ET-1 production by prostate adenocarcinoma cells. In PC-3 and DU145 cells, ET-1 gene expression and secretion were up-regulated by TGFβ-1, EGF and IL1-α, whereas IGF-1 was ineffective. Conversely, none of the treatments affected ECE-1 or ET-3 gene expression. CONCLUSIONS. In conclusion, ET-1 production by prostate adenocarcinoma cells is downregulated by androgens and up-regulated by factors involved in tumour progression indicating a role for this peptide in the biology of prostate cancer. In view of the role exerted by ET-1 in the process of bone metastasis, our data suggest the use of ET-1 receptor antagonists in the treatment of advanced prostate cancer.

Original languageEnglish
Pages (from-to)267-277
Number of pages11
JournalProstate
Volume49
Issue number4
DOIs
Publication statusPublished - 2001

    Fingerprint

Keywords

  • Androgen receptor
  • Bone metastasis
  • Endothelin-1
  • Growth factor
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this