PA28-gamma is the activator of
20S proteasome, the
ATP-dependent proteolytic system that plays an important role in cell cycle progression in various cell types. In this paper, we show the abnormally high expression of PA28-gamma in various
thyroid neoplasms. Thyroid samples were obtained from patients with normal thyroid (4 cases) and with the following diseases:
papillary adenocarcinoma (13 cases), multinodular
goiter (4 cases), and
anaplastic carcinoma (1 case). PA28-gamma expression was estimated by immunohistochemical staining and Western blotting. In all of the
papillary adenocarcinoma samples, PA28-gamma was abnormally overexpressed, especially in
cancer cells existing at the peripheral region of the
cancer mass or in
cancer cells invading the capsular region surrounding the
cancer mass. In
cancer cells of these areas, PA28-gamma was predominantly distributed in nucleus rather than in the cytoplasm of
cancer cells. On the other hand, no obvious PA28-gamma expression was observed in the adjacent normal thyroid follicular cells. In multinodular
goiter, the expression of PA28-gamma was relatively low compared with
papillary adenocarcinoma. In
anaplastic carcinoma, PA28-gamma was expressed at the highest level, especially in poorly differentiated regions such as squamous
metaplasia of anaplastic
cancer tissue. Therefore, the PA28-gamma expression seems to be restricted to
thyroid cancer cells, especially in the region where the growth rate of
cancer cells is accelerated. This result is further confirmed by the fact that C2, alpha-subunit of
20S proteasome, and
proliferating cell nuclear antigen are similarly overexpressed in this region. Thus, PA28-gamma might be involved in the regulatory system for the cell cycle. Moreover, the growth of
thyroid cancer cell lines was affected by the
proteasome inhibitor,
clasto-lactacystin beta-lactone. These results demonstrate that PA28-gamma is overexpressed in
thyroid cancer, especially in its growth-accelerated cells.