Role of the endothelin axis in the proliferation of human thyroid cancer cells

Julian E Donckier, Jeannine Mertens-Strijthagen, Bruno Flamion
Clinical Endocrinology 2007, 67 (4): 552-6

OBJECTIVE: Endothelin-1 (ET-1) may play a role in carcinogenesis. ET-1 axis is overexpressed in thyroid carcinoma. We investigated the expression and the production of ET-1 by thyroid cancer cells as well as the effect of ET-1 receptor antagonism on cell proliferation.

DESIGN: Human papillary and follicular thyroid carcinoma cell lines were cultured.

MEASUREMENTS: (i) Prepro-ET-1, ET-1 receptors (ETA R and ETB R) and ET-1 converting enzyme (ECE) by reverse transcriptase polymerase chain reaction (RT-PCR); (ii) the presence of ETA R by western blot; (iii) ET-1 concentrations in medium by an enzyme immunometric assay; (iiii) the proliferation of cells by BrdU and tritiated thymidine incorporation.

RESULTS: RT-PCR detected the presence of mRNA for prepro-ET-1, ETA R and ECE in papillary and follicular carcinoma cells. ETB R was only expressed by follicular cells. ETA R was also detected in both cell types by western blot. Measurements of ET-1 concentrations demonstrated a secretion of active ET-1 by the cells. ETA R antagonism with atrasentan reduced cell proliferation by 16% in papillary carcinoma cells (P < 0.05) and by 51% in follicular carcinoma cells (P < 0.001).

CONCLUSIONS: Papillary and follicular carcinoma cells express all components of the ET-1 axis. ETA R antagonism exerts antiproliferative effects, which opens up new therapeutic perspectives in thyroid carcinoma.

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