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

Julian E. Donckier

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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Jeannine Mertens-Strijthagen,

Jeannine Mertens-Strijthagen

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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Bruno Flamion,

Bruno Flamion

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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Julian E. Donckier,

Julian E. Donckier

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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Jeannine Mertens-Strijthagen,

Jeannine Mertens-Strijthagen

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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Bruno Flamion,

Bruno Flamion

Molecular Physiology Research Unit, Laboratory of Physiology and Pharmacology, FUNDP, University of Namur, Namur, Belgium

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First published: 24 May 2007

https://doi.org/10.1111/j.1365-2265.2007.02923.x

Citations: 8

Julian Donckier, Department of Internal Medicine and Endocrinology, University Hospital of Mont-Godinne, B-5530 Yvoir, Belgium. Tel.: +32 81 42 32 81; Fax: +32 81 42 32 83; E-mail: [email protected]

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Summary

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 (ET_A R and ET_B R) and ET-1 converting enzyme (ECE) by reverse transcriptase polymerase chain reaction (RT-PCR); (ii) the presence of ET_A 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, ET_A R and ECE in papillary and follicular carcinoma cells. ET_B R was only expressed by follicular cells. ET_A 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. ET_A 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. ET_A R antagonism exerts antiproliferative effects, which opens up new therapeutic perspectives in thyroid carcinoma.

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Volume67, Issue4

October 2007

Pages 552-556

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

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

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