Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation
Open Access
- 10 October 2005
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 118 (7), 1645-1652
- https://doi.org/10.1002/ijc.21525
Abstract
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 (ETAR) and endothelin‐B receptor (ETBR)) 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, ETAR, ETBR and all endothelin‐converting enzyme‐1 (ECE‐1) isoforms in oral SCC cells, but only the expression of ET‐1, ETBR and ECE‐1 was increased when compared to normal human epidermal keratinocytes. ET‐1 alone stimulated proliferation of oral SCC cells. Antagonists of either ETAR or ETBR 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.Keywords
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