Identification of Novel Genes Responsible for Tumorigenesis and Growth in Lactotroph PitNET

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17544
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nippon Medical School
• Principal Investigator: Hattori Yujiro 日本医科大学, 医学部, 講師 (40528436)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 下垂体 / 下垂体腫瘍 / 神経内分泌学 / 遺伝子解析

Outline of Final Research Achievements

RNA sequencing analysis was performed on surgical specimens from lactotroph pituitary neuroendocrine tumor (lactotroph PitNET) that had not been treated with dopamine agonists or other drugs prior to surgery. The results revealed a different gene expression pattern in lactotroph PitNET compared to the normal pituitary, with 1275 up-regulated genes and 2153 down-regulate genes identified. The top 30 differential expression genes contained 9 inter-long noncoding RNAs. Integrity Pathway analysis revealed activation of estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling.

Free Research Field

神経内分泌学

Academic Significance and Societal Importance of the Research Achievements

既報でもプロラクチン産生下垂体神経内分泌腫瘍の発現遺伝子を検討した研究の報告はあるが、いずれも術前に薬剤治療を受け、それにより遺伝子発現に影響を及ぼした腫瘍を扱ったものであった。本研究は術前に薬剤治療を受けていない、すなわち腫瘍における遺伝子発現が薬剤修飾を受けていない腫瘍のみ選択し解析したことに新規性がある。本研究で明らかになった発現変動遺伝子はプロラクチン産生下垂体神経内分泌腫瘍の治療ターゲットとなりうる可能性があり、本研究成果の意義は高いと考える。