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Endothelin-1 promotes cell survival in renal cell carcinoma through the ET(A) receptor

Beth R Pflug1, Hong Zheng, Michael S Udan

  • 1Department of Urology, University of Pittsburgh, Pittsburgh, PA 15213, USA. pflugbr@upmc.edu

Cancer Letters
|April 4, 2006
PubMed

Insights

Endothelin-1 (ET-1) impacts kidney cancer. Targeting the ET(A) receptor may offer a new treatment strategy by blocking ET-1's protective effect on renal cell carcinoma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Endothelin-1 (ET-1) is a vasoconstrictor influencing benign and malignant tissues via ET(A) and ET(B) receptors.
  • ET-1 plays a role in normal and diseased kidney function.
  • Renal cell carcinoma (RCC) is a significant malignancy affecting the kidney.

Purpose of the Study:

  • To investigate the expression and function of the endothelin axis in renal cell carcinoma (RCC).
  • To explore the potential of targeting the endothelin axis for RCC treatment.

Main Methods:

  • Quantitative RT-PCR and Southern analyses to detect ET-1 and its receptors (ET(A), ET(B)) mRNA expression in RCC cell lines.
  • Analysis of ET(B) promoter (EDNRB) methylation in RCC cell lines and patient tissues.
  • Assessing the functional impact of ET-1 on paclitaxel-induced apoptosis in RCC cells via the PI3-kinase/Akt pathway.

Main Results:

  • High levels of ET-1 and ET(A) receptor mRNA were detected in all investigated RCC cell lines.
  • ET(B) mRNA was expressed in some RCC cell lines, with promoter methylation observed in others and in patient tumor samples.
  • ET-1 inhibited paclitaxel-induced apoptosis in RCC cells, mediated by ET(A) and the PI3-kinase/Akt pathway.

Conclusions:

  • The endothelin axis, particularly ET(A) receptor signaling, is active in renal cell carcinoma.
  • ET-1 promotes RCC cell survival by inhibiting apoptosis through the ET(A)/PI3-kinase/Akt pathway.
  • Targeting the ET(A) receptor presents a promising therapeutic strategy for renal cell carcinoma.

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