Identification of estrogen receptor variant expression profile in hormone-sensitive tumor

• Project/Area Number: 17K16171
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Nippon Medical School
• Principal Investigator: Hattori Yujiro 日本医科大学, 医学部, 講師 (40528436)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 下垂体腫瘍 / エストロゲン受容体 / digital PCR / 神経内分泌学 / 内分泌学

Outline of Final Research Achievements

We quantitatively assessed the expression profiles of estrogen receptor (ER) transcripts and proteins in pituitary tumor samples, using reverse transcription-digital polymerase chain reaction and immunohistochemistry, and further investigated the correlations between the expression levels of ER and those of downstream responsive genes. Regardless of the type of pituitary tumor, ERα variants and ERβ were barely observed. The detailed analysis limited to non-functional adenomas exhibited a biphasic wild type ERα expression pattern and were categorized into significantly different high- and low- ERα expression level groups. Similar results were obtained through the immunohistochemical staining of NFPAs. The expression levels of ESR1 positively correlated with those of GREB1, the estrogen-responsive gene.

Academic Significance and Societal Importance of the Research Achievements

本研究により下垂体腫瘍におけるdigital PCRを用いた全長型および変異型のエストロゲン受容体（ER）の遺伝子発現量を測定する定量系を確立した。それを用いた解析により下垂体腫瘍ではERα変異体の発現プロファイルが初めて判明した。本研究は、エストロゲン感受性腫瘍である乳癌や、アンドロゲン依存性の前立腺腫瘍などエストロゲン以外のホルモン感受性腫瘍の発現にも応用できる可能性が示唆され、成果の意義は高いと考える。