Aberrant apoptosis in thyroid epithelial cells from goiter nodules

E. Mezősi, Hiroko Yamazaki, James D. Bretz, Su He Wang, Patricia L. Arscott, Saho Utsugi, Paul G. Gauger, Norman W. Thompson, James R. Baker

Research output: Contribution to journalArticle

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Abstract

The specific pathogenesis of nodular goiter and the role of apoptosis in goitrogenesis are not known. We sought to examine the regulation of the TNF-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL)-induced apoptosis pathways in primary thyroid cells from 17 patients with nodular goiter, using 10 normal thyroids as controls. Both goitrous and normal thyroid cells were resistant to recombinant human TRAIL and an agonist anti-Fas antibody under basal conditions. However, all normal thyrocytes could be sensitized by TNFα/IL-1β or interferon γ/IL-1β to undergo apoptosis in response to TRAIL or FasL, respectively. In contrast, the majority of goiter-derived cells remained resistant to TRAIL (12 of 17 samples) or FasL (9 of 17 samples) after cytokine pretreatment; 14 of 17 goiter nodules were resistant to at least one death ligand. Goiter size was inversely correlated with the sensitivity to TRAIL-mediated apoptosis. The resistance of goiter cells to TRAIL did not appear to be due to transcriptional regulation or cell surface expression of death and decoy receptors. However, increased proteasome activity was found in a subset of goiter cells resistant to both death ligands, and proteasome inhibitors could sensitize these goiter cells to TRAIL-mediated apoptosis. In conclusion, goiter-derived thyroid cells are resistant to TRAIL and/or Fas-induced apoptosis in vitro, and this may represent a new aspect of aberrant growth regulation in goiter nodules. The increased proteasome activity associated with this resistance suggests that the proteasome may be an important regulator of apoptosis in nodular goiter.

Original languageEnglish
Pages (from-to)4264-4272
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number9
DOIs
Publication statusPublished - Sep 2002

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
Goiter
Apoptosis
Nodular Goiter
Fas Ligand Protein
Thyroid Gland
Proteasome Endopeptidase Complex
Interleukin-1
Ligands
Death Domain Receptors
Proteasome Inhibitors
Thyroid Epithelial Cells
Epithelial Cells
Interferons
Anti-Idiotypic Antibodies
Cytokines
Antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Mezősi, E., Yamazaki, H., Bretz, J. D., Wang, S. H., Arscott, P. L., Utsugi, S., ... Baker, J. R. (2002). Aberrant apoptosis in thyroid epithelial cells from goiter nodules. Journal of Clinical Endocrinology and Metabolism, 87(9), 4264-4272. https://doi.org/10.1210/jc.2002-020111

Aberrant apoptosis in thyroid epithelial cells from goiter nodules. / Mezősi, E.; Yamazaki, Hiroko; Bretz, James D.; Wang, Su He; Arscott, Patricia L.; Utsugi, Saho; Gauger, Paul G.; Thompson, Norman W.; Baker, James R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 9, 09.2002, p. 4264-4272.

Research output: Contribution to journalArticle

Mezősi, E, Yamazaki, H, Bretz, JD, Wang, SH, Arscott, PL, Utsugi, S, Gauger, PG, Thompson, NW & Baker, JR 2002, 'Aberrant apoptosis in thyroid epithelial cells from goiter nodules', Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 9, pp. 4264-4272. https://doi.org/10.1210/jc.2002-020111
Mezősi, E. ; Yamazaki, Hiroko ; Bretz, James D. ; Wang, Su He ; Arscott, Patricia L. ; Utsugi, Saho ; Gauger, Paul G. ; Thompson, Norman W. ; Baker, James R. / Aberrant apoptosis in thyroid epithelial cells from goiter nodules. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 9. pp. 4264-4272.
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