これまでの臨床的知見から子宮体癌担癌状態では着床が成立しないことが知られている。そこで、子宮体癌由来細胞株よりリプログラミング細胞を作製し、DNAのメチル化および着床能変化を解析することで子宮体癌における着床阻止メカニズムの探索を目的とした。
作製された(Reprogrammed-Cancer cells, RC細胞)は未分化マーカーの発現上昇や、in vitro着床試験による着床能の亢進が認められた。また、DNAメチル化アレイ解析から親株とRC細胞間で4.2% (31,511/747,192) のCpGに有意なメチル化率の差が認められた(p<0.05, |β|>0.25)。
Clinical observations have confirmed that implantation does not occur in patients with endometrial cancer. The mechanism of acquisition of phenotypes characteristic of cancer cells can be examined by identifying epigenomic changes during reprogramming. Therefore, we first produced reprogrammed cancer (RC) cells from human endometrial cancer cell lines. DNA methylation and changes in gene expression and implantation capacity in these cells were then examined to explore the mechanism of inhibition of implantation in endometrial cancer.
Upregulation of undifferentiated markers and decreased cell proliferation were observed in the RC cells. The in vitro implantation test showed significantly increased implantation capacity in RC cells compared with parent cell lines (p<0.05). DNA methylation array analysis showed significant differences in methylation (31,511/747,192, 4.2%) in parent and RC cells (p<0.05, |β|>0.25). A calcium signaling pathway was identified by KEGG enrichment analysis.

研究種目 : 基盤研究 (C) (一般)
研究期間 : 2018～2020
課題番号 : 18K09272
研究分野 : 婦人科腫瘍学