Establishment of in vitro carcinogenesis model of endometriosis related ovarian carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shimane University
• Principal Investigator: Nakayama Kentaro 島根大学, 医学部, 准教授 (70346401)
• Co-Investigator(Kenkyū-buntansha): 京 哲 島根大学, 医学部, 教授 (50272969)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 卵巣癌 / 明細胞癌 / ARID1A / 発癌 / 癌遺伝子

Outline of Final Research Achievements

To clarify minimal requirement for carcinogenesis, we sought to establish an in vitro stepwise carcinogenesis model using immortalized endometriotic epithelial cells with overexpressed cyclinD1/cdk4 and hTERT, in which we additionally introduced selected genetic elements frequently observed in clinical samples. Mutational analysis using clinical samples of ovarian clear cell and endometrioid adenocarcinomas identified frequent ARID1A mutations (90%) and p53 mutations (20%), but their overlap was relatively rare. Thus, we introduced ARID1A knock out in combination with oncogenic mutant KRAS allele into immortalized cells, exhibit tumorigenic phenotypes. Additional introduction of genetic factors will be attempted to investigate in vitro and in vivo tumorigenicity, and c-Myc overexpression, mutant PIC3CA, or phosphorylated Akt (p-Akt) are going to transfect to immortalized endometriotic epithelial cells.

Free Research Field

婦人科腫瘍学