Low expression of endothelin receptor B (EDNRB) is related to H3K9me3 binding with the EDNRB promoter region and is associated with the clinical T tumor stage in salivary adenoid cystic carcinoma

• Published in: Oral surgery, oral medicine, oral pathology and oral radiology oral medicine, oral pathology and oral radiology, 2015-08, Vol.120 (2), p.258-268
• Main Authors: Xia, Rong-Hui, DDS, Wang, Zhen, DDS, Zhang, Chun-Ye, DDS, PhD, Hu, Yu-Hua, DDS, PhD, Zhou, Rong-Rui, DDS, Wang, Li-Zhen, DDS, Tian, Zhen, DDS, PhD, Li, Jiang, DDS, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - metabolism; Carcinoma, Adenoid Cystic - metabolism; Carcinoma, Adenoid Cystic - pathology; Dentistry; Female; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Promoter Regions, Genetic; Receptor, Endothelin B - metabolism; Salivary Gland Neoplasms - metabolism; Salivary Gland Neoplasms - pathology; Signal Transduction; Surgery
• ISSN: 2212-4403; 2212-4411
• DOI: 10.1016/j.oooo.2015.04.015

Objective To investigate the endothelin receptor B (EDNRB) expression in salivary adenoid cystic carcinoma (ACC) and the mechanism of the regulation of EDNRB expression. Study Design After screening, EDNRB was selected, and the expression was detected using immunohistochemistry in 33 ACC samples (including 6 clinical tumor stage 1 [T1] patients, 13 T2 patients, 9 T3 patients, and 5 T4 patients) and 20 adjacent glands. Interaction between the EDNRB promoter region and histone H3 lysine 9 trimethylation (H3K9me3) was examined using chromatin immunoprecipitation (ChIP) in combination with ChIP–polymerase chain reaction (ChIP-PCR). EDNRB expression in ACC cells treated with chaetocin was detected using quantitative real-time PCR (qRT-PCR) and Western blot tests. Results EDNRB expression was lower in ACC than that in adjacent glands ( P  = .006). The expression of EDNRB in patients with advanced T stage was lower than that in patients with early T stage ( P  = .024). The low EDNRB gene expression group had more H3K9me3 binding regions in the gene promoter ( P  = .003). EDNRB gene expression significantly increased in the ACC cell lines after treatment with chaetocin. Chaetocin could reduce the interaction between the EDNRB promoter and H3K9me3. Conclusions H3K9me3 binding to the EDNRB promoter region could reduce the EDNRB expression. Low EDNRB expression played a role in the progression of ACC tumors.