Transcriptomic analysis of hormone-sensitive patient-derived endometrial cancer spheroid culture defines Efp as a proliferation modulator.
Estrogen-responsive endometrial cancer (EC) is prevalent in uterine cancer. Its precise molecular mechanisms remain to be elucidated partly because of limited availability of estrogen-sensitive EC models recapitulating clinical pathophysiology. We previously established EC patient-derived cancer cell (EC-PDC) spheroid culture with high expression of estrogen receptor α (ERα). Using this EC-PDC, we study the transcriptional regulation and function of estrogen-responsive finger protein (Efp), a prototypic tripartite motif (TRIM) protein that modulates protein degradation and RNA processing. Intense estrogen-dependent EFP mRNA induction and high ERα occupancy to EFP estrogen responsive element (ERE) were observed in EC-PDC. Luciferase reporter gene assay showed that the ERE facilitates EFP transcriptional activity estrogen-dependently. siRNA-mediated Efp silencing in EC-PDC resulted in suppressed spheroid proliferation and altered gene expression profile, featuring downregulation of genes related to cell cycle (e.g., CDK6) and inflammation/immune responses (e.g., IL10RA, IL26, and IL6ST) while unaffected expression of cancer stemness-related markers. Taken together, EC-PDC spheroid culture is a powerful EC tool that enables to dissect Efp-mediated ERα signaling pathways as an estrogen-sensitive EC model. This study provides an insight into alternative EC therapeutic strategies targeting ERα-Efp axis.
['Yang|Chiujung|C|', 'Ikeda|Kazuhiro|K|', 'Horie-Inoue|Kuniko|K|', 'Sato|Wataru|W|', 'Hasegawa|Kosei|K|', 'Takeda|Satoru|S|', 'Itakura|Atsuo|A|', 'Inoue|Satoshi|S|']
D001483:Base Sequence D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D016889:Endometrial Neoplasms D047628:Estrogen Receptor alpha D004967:Estrogens D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D018874:Spheroids, Cellular D014157:Transcription Factors D014158:Transcription, Genetic D000070584:Tripartite Motif Proteins D044767:Ubiquitin-Protein Ligases
Endometrial cancer Estrogen Estrogen-responsive finger protein (Efp) Cyclin dependent kinase 6 (CDK6) Patient-derived cancer cell (PDC)