A Novel Pathogenesis Mechanism of Endometrial Adenocarcinoma with Endometrial atypical proliferation as the place of origin

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18194
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Okada Tadahi 札幌医科大学, 医学部, 研究員 (30867453)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: タイト結合 / シグナル伝達 / claudin

Outline of Final Research Achievements

There are various types of uterine cancer, including endometrial adenocarcinoma and serous adenocarcinoma, with endometrial adenocarcinoma being the histologic type that accounts for more than 80% of uterine cancers. Endometrial adenocarcinoma is thought to originate from endometrial atypical proliferation due to high expression of claudin-2, a leaky tight-binding molecule that is closely related to cancer cell growth.
In this study, we analyzed the regulatory mechanism of claudin-2 expression and elucidated the carcinogenic process from endometrial atypical hyperplasia to endometrial carcinoma.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、リーキータイプのタイトジャンクションタンパク質であるCLDN-2の過剰発現が、ヒト子宮内膜腺癌の悪性化に密接に寄与していることを初めて明らかにした。またこのダウンレギュレーションが上皮のバリアを上昇させ、子宮内膜がん細胞の細胞増殖だけでなく、細胞移動や細胞浸潤も抑制し、新規治療薬の標的になりうることが示された。