Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE-1 blocks cell proliferation

Int J Cancer. 2006 Apr 1;118(7):1645-52. doi: 10.1002/ijc.21525.


The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin-1 (ET-1), its receptors (endothelin-A receptor (ET(A)R) and endothelin-B receptor (ET(B)R)) and isoforms of its specific converting enzyme (ECE-1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE-specific inhibitor (ECE-i) and siRNA targeting of the ECE-1 gene on SCC cell proliferation. We observed the expression of ET-1, ET(A)R, ET(B)R and all endothelin-converting enzyme-1 (ECE-1) isoforms in oral SCC cells, but only the expression of ET-1, ET(B)R and ECE-1 was increased when compared to normal human epidermal keratinocytes. ET-1 alone stimulated proliferation of oral SCC cells. Antagonists of either ET(A)R or ET(B)R inhibited ET-1-mediated proliferation. Decreased ECE-1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE-i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid Endopeptidases / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Proliferation*
  • Endothelin-1 / analysis
  • Endothelin-1 / biosynthesis*
  • Endothelin-Converting Enzymes
  • Humans
  • Metalloendopeptidases / metabolism
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / physiopathology*
  • Protein Isoforms
  • RNA, Small Interfering
  • Receptor, Endothelin A / analysis
  • Receptor, Endothelin A / biosynthesis*
  • Receptor, Endothelin B / analysis
  • Receptor, Endothelin B / biosynthesis*
  • Tumor Cells, Cultured


  • Endothelin-1
  • Protein Isoforms
  • RNA, Small Interfering
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • ECE1 protein, human
  • Endothelin-Converting Enzymes