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Aberrant apoptosis in thyroid epithelial cells from goiter nodules
Emese Mezosi1, Hiroko Yamazaki, James D Bretz
1Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0648, USA.
The Journal of Clinical Endocrinology and Metabolism
|September 6, 2002
Summary
Thyroid cells from nodular goiters resist apoptosis induced by death ligands (TRAIL, FasL). Increased proteasome activity in these cells suggests a novel mechanism for aberrant growth in goiter nodules.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Medicine
Background:
- The pathogenesis of nodular goiter and the role of apoptosis remain unclear.
- Understanding apoptosis regulation is crucial for goiter pathogenesis.
Purpose of the Study:
- To investigate the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways in nodular goiter.
- To explore the role of apoptosis resistance in goiter formation.
Main Methods:
- Primary thyroid cells from 17 nodular goiter patients and 10 controls were used.
- Cells were treated with TRAIL, anti-Fas antibody, and cytokines (TNFα/IL-1β, IFNγ/IL-1β).
- Proteasome activity was assessed, and proteasome inhibitors were used.
Main Results:
- Goiter cells showed resistance to TRAIL and FasL-induced apoptosis, even after cytokine sensitization.
- Goiter size correlated inversely with TRAIL-mediated apoptosis sensitivity.
- Increased proteasome activity was observed in resistant goiter cells, which could be sensitized by proteasome inhibitors.
Conclusions:
- Thyroid cells from nodular goiters exhibit resistance to TRAIL and FasL-induced apoptosis.
- This resistance may contribute to aberrant growth regulation in goiter nodules.
- Elevated proteasome activity is implicated as a key regulator of apoptosis resistance in nodular goiter.