Development of new molecular targeted drugs targeting EMT-related genes in endometrial cancer

Research Project

Project/Area Number	15K10728
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Obstetrics and gynecology
Research Institution	Keio University
Principal Investigator	Kataoka Fumio 慶應義塾大学, 医学部(信濃町), 助教 (40306824)
Research Collaborator	TANAKA Hideo
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	子宮体部癌肉腫 / EMT / 分子標的
Outline of Final Research Achievements	Uterine carcinosarcoma is reported to undergo epithelial to mesenchymal transition (EMT). The gene expression profiles of uterine carcinosarcoma, endometrial cancer, and uterine sarcoma were compared and evaluated the role of EMT and chromosomal aberrations in uterine carcinosarcoma tumor formation. The expression of 39 EMT-related genes and evaluated TGF-beta signaling by phospho-SMAD2/3 (p-SMAD2/3) staining were examined. Acquired markers of EMT were upregulated in uterine carcinosarcoma. Based on the expression profile, uterine carcinosarcoma resembles uterine sarcoma rather than endometrial cancer. Immunohistochemistry showed that carcinomatous region of uterine carcinosarcoma have higher expression of p-SMAD2/3 than endometrial cancer. TGF-beta signaling is activated in uterine carcinosarcoma, which suggest that this may contribute to high expression of TGF-beta and thereby EMT phenotype of uterine carcinosarcoma.