Endothelin-1 inhibits apoptosis in prostate cancer

Joel B. Nelson, Michael S. Udan, Georgi Guruli, Beth Pflug

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Endothelin-1 (ET-1), produced by the prostate epithelia, likely plays an important role in the progression of prostate cancer. ET-1 can bind two receptor subtypes; generally, binding of the endothelin receptor A (ETA) induces a survival pathway, whereas binding of the endothelin receptor B (ETB) mediates clearance of circulating ET-1 as well as promotes apoptosis. In prostate carcinoma, hypermethylation of the ETB promoter results in repression of ETB expression, thereby eliminating the negative growth response that ET-1 binding elicits through this receptor. Therefore, activation of ETA exclusively provides a pathway for survival advantage. Our current studies examine the mechanisms by which activation of the ETA may allow growth/survival. ET-1 treatment of prostate tumor cells significantly decreased paclitaxel-induced apoptosis through activation of the ETA subtype. The anti-apoptotic effects of ET-1 are mediated, at least in part, through the Bcl-2 family. Although no significant changes in Bcl-2 expression occurred with ET-1 treatment, the pro-apoptotic family members Bad, Bax, and Bak all decreased significantly. Further analysis of the survival pathway demonstrated that phosphorylation of Akt occurs with ET-1 treatment in a time- and dose-dependent manner through phosphatidyinositol 3-kinase activation. These data support the combination of ETA antagonists and apoptosis-inducing therapies for prostate cancer treatment.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalNeoplasia
Volume7
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Endothelin-1
Prostatic Neoplasms
Apoptosis
Endothelin A Receptors
Endothelin B Receptors
Prostate
Survival Analysis
Growth
Paclitaxel
Phosphotransferases
Epithelium
Phosphorylation
Carcinoma

Keywords

  • AKT
  • Apoptosis
  • Endothelin receptors
  • Endothelin-1
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research

Cite this

Endothelin-1 inhibits apoptosis in prostate cancer. / Nelson, Joel B.; Udan, Michael S.; Guruli, Georgi; Pflug, Beth.

In: Neoplasia, Vol. 7, No. 7, 07.2005, p. 631-637.

Research output: Contribution to journalArticle

Nelson, JB, Udan, MS, Guruli, G & Pflug, B 2005, 'Endothelin-1 inhibits apoptosis in prostate cancer', Neoplasia, vol. 7, no. 7, pp. 631-637. https://doi.org/10.1593/neo.04787
Nelson, Joel B. ; Udan, Michael S. ; Guruli, Georgi ; Pflug, Beth. / Endothelin-1 inhibits apoptosis in prostate cancer. In: Neoplasia. 2005 ; Vol. 7, No. 7. pp. 631-637.
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