Bcl‐2 is a prognostic marker and its silencing inhibits recurrence in ameloblastomas

• Published in: Oral diseases 2019-05, Vol.25 (4), p.1158-1168
• Main Authors: Kim, Jue Young, Kim, Jinsun, Bazarsad, Shadavlonjid, Cha, In‐Ho, Cho, Sung‐Won, Kim, Jin
• Format: Article
• Language: English
• Subjects: Adult; Ameloblastoma; Ameloblastoma - genetics; Ameloblastoma - pathology; Animals; Apoptosis; Bcl‐2; Data processing; Dentistry; Female; Flow cytometry; Humans; Immunodeficiency; Jaw Neoplasms - genetics; Jaw Neoplasms - pathology; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - genetics; Male; Mice; Middle Aged; Neoplasm Recurrence, Local; Nodules; OPG; Osteoprotegerin; Osteoprotegerin - genetics; Patients; Prognosis; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - blood; Proto-Oncogene Proteins c-bcl-2 - metabolism; recurrence; siRNA; Therapeutic applications; Transfection; Tumors; Western blotting
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.13070

Objectives Ameloblastomas are the most common odontogenic epithelial tumors with high recurrence rate. The aim of this study was to identify apoptosis‐related genes with recurrence of ameloblastomas and to evaluate its feasibility as a prognostic marker and as a target molecule preventing from recurrence. Materials and Methods Public microarray data were analyzed. To evaluate their expression in ameloblastoma patients, immunohistochemical staining was performed in 89 human ameloblastoma tissues. Quantitative PCR was performed by use of ameloblastoma cell line (AM‐1). Fluorescence activated cell sorting analysis and western blotting were conducted following transfection with siRNA. Further, AM‐1 cells were implanted in the renal subcapsular layer of immunodeficient mice. Results Microarray data analysis revealed that osteoprotegerin (OPG) and B‐cell lymphoma 2 (Bcl‐2) were the two most upregulated genes in ameloblastoma. Only Bcl‐2 expression was significantly (p = 0.020) associated with recurrence in conservative treatment group (n = 17) among 89 patients. Silencing of Bcl‐2 increased apoptosis in AM‐1 cells in vitro and inhibited tumor nodule formation of AM‐1 cells in vivo. Conclusion These results suggest that Bcl‐2 expression is a useful biomarker to predict recurrence of ameloblastomas, and as a therapeutic target molecule to prevent recurrence of ameloblastoma.