endothelin-1 and Adenocarcinoma--Follicular

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.. Human papillary and follicular thyroid carcinoma cell lines were cultured.. (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.. 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).. 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.

Topics: Adenocarcinoma, Follicular; Aspartic Acid Endopeptidases; Atrasentan; Blotting, Western; Bromodeoxyuridine; Carcinoma, Papillary; Cell Line, Tumor; Cell Proliferation; Endothelin A Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Humans; Immunoradiometric Assay; Metalloendopeptidases; Pyrrolidines; Receptor, Endothelin A; Receptor, Endothelin B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thymidine; Thyroid Neoplasms