Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas

作者：Wang, Fei; Gao, Hua; Li, Chuzhong; Bai, Jiwei; Lu, Runchun; Cao, Lei; Wu, Yongtu; Hong, Lichuan; Wu, Yonggang; Lan, Xiaolei; Zhang, Yazhuo^*

来源：Journal of Neuro-Oncology, 2014, 116(1): 83-88.

DOI：10.1007/s11060-013-1276-2

• Prolactinoma
• Resistance
• Recurrence
• PRB3 mRNA
• Whole-exome sequencing

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

• 出版日期2014-1
• 单位青岛大学; 清华大学; 北京市神经外科研究所; 首都医科大学; 新疆维吾尔自治区人民医院