Context: We previously showed that BAG3 protein, a member of the BAG (Bcl-2- Associated Athanogene) co-chaperone family, modulates apoptosis in human leukemias. The expression of BAG3 in other tumor types has not been extensively investigated so far.

Objective: The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to Tumor Necrosis Factor- Related Apoptosis- Inducing Ligand (TRAIL).

Design, Setting, and Patients: We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering (si)RNA on TRAIL- induced apoptosis in NPA cells. Subsequently, we analyzed BAG3 expression in 30 benign lesions and 56 carcinomas from patients of the Naples Tumor Institute Fond. Sen. Pascale.

Main outcome measures: the main outcome measures were: analysis of BAG3 protein in NPA cells by western blot and immunocytochemistry; analysis of apoptosis in TRAIL- stimulated NPA cells by flow cytometry; evaluation of BAG3 expression in specimens from thyroid lesions by immunohistochemistry.

Results: BAG3 was expressed in human thyroid carcinoma cell lines; siRNA- mediated downmodulation of its levels significantly (P < 0.0195) enhanced NPA cell apoptotic response to TRAIL. The protein was not detectable in 19/20 specimens of normal thyroid or goiters, while 54 of 56 analyzed carcinomas (15 follicular, 28 papillary and 13 anaplastic) were clearly positive for BAG3 expression.

Conclusions: BAG3 downmodulates the apoptotic response to TRAIL in human neoplastic thyroid cells. The protein is specifically expressed in thyroid carcinomas and not in normal thyroid tissue or goiter.