Potential roles for PA28beta in gastric adenocarcinoma development and diagnosis.

PURPOSE

This study aimed to investigate the expression level of human proteasome activator PA28beta subunit (PA28beta) in gastric adenocarcinomas (GA) tissues and investigate its potential role in GA carcinogenesis.

METHODS

To investigate the expression profile of PA28beta in patients with GA, we employed immunohistochemistry for detection of 287 cases of paired GA and adjacent non-neoplastic tissues. To evaluate the role of PA28beta in GA cells, we measured cell growth, colony formation, soft agar, and nude mice tumorigenicity assays in MKN-45 GA cells pre- and post-PA28beta transfection.

RESULTS

PA28beta had lower expression in 183 of 287 GA cases compared to paired normal samples (63.76%; P < or = 0.001). Decreased expression was dependent on histological type, TNM stage, and differentiation grade. Significantly decreased expression was correlated with a diffuse histological type (88/116, 75.86%) compared to an intestinal type (84/152, 55.26%; P < or = 0.001), with advanced TNM stages (T3: 44/59, 74.58%; T4:25/32, 78.13%) compared to earlier stages (T1: 25/47, 53.19%; T2: 90/149, 60.40%; P = 0.004), and poorer differentiation grade (poor: 68/90, 75.56%) compared to a higher grade (high: 9/18, 50%, moderate: 74/134, 55.22%) (P = 0.006). Over-expression of PA28beta inhibited cell growth, proliferation, and tumorigenicity of MKN-45 GA cells.

CONCLUSIONS

These results indicated that PA28beta might participate in the origin and progression of GA cancer through changes to cell proliferation activity and tumorigenicity. Therefore, PA28beta might be a novel biomarker for GA.