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


METHODS
Human papillary and follicular thyroid carcinoma cell lines were cultured.


METHODS
(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.
Donckier
Julian E
JE
Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium. julian.donckier@mint.ucl.ac.be
Mertens-Strijthagen
Jeannine
J
Flamion
Bruno
B
D018263:Adenocarcinoma, Follicular / Q000378:metabolism / Q000473:pathology*; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000235:genetics; D000077868:Atrasentan; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D015592:Immunoradiometric Assay; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D044022:Receptor, Endothelin A / Q000032:analysis / Q000235:genetics; D044023:Receptor, Endothelin B / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D001973:Bromodeoxyuridine; D000077868:Atrasentan; D013936:Thymidine