Experimental analysis of the molecular carcinogenesis of ovarian high grade serous carcinoma originated from fallopian tubes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04985
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shimane University
• Principal Investigator: KYO SATORU 島根大学, 医学部, 教授 (50272969)
• Co-Investigator(Kenkyū-buntansha): 中山 健太郎 島根大学, 医学部, 准教授 (70346401)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 卵巣漿液性癌 / 発癌分子機構 / 卵管采

Outline of Final Research Achievements

To identify the molecular requirements for the carcinogenesis of ovarian high grade serous carcinoma (HGSC), we first propagated primary fimbria epithelial cells, which were obtained, isolated and purified from surgical specimens of fallopian tubes. Next, we introduced cyclin D1/cdk4 as well as hTERT expression vectors into these cells via lentivirus and finally obtained immortal cells with sustaining morphological features of original fimbria cells. Based on the comprehensive gene mutation analysis using clinical samples, we listed up the candidate driver gene mutations in HGCS. Among them, we challenged to mimic these genetic alterations in immortalized fimbria cells. Our result showed that 3 steps; p53 gene mutation, KRAS gene mutation, activation of either RAS-ERK or PIK3-AKT pathway, are required and sufficient for immortalized cells to obtain tumorigenic phenotypes. Knowledge of these molecular steps will be useful to develop novel molecular target therapies for HGSC.

Free Research Field

婦人科腫瘍学