RRC ID 33973
著者 Suzuki E, Kajita S, Takahashi H, Matsumoto T, Tsuruta T, Saegusa M.
タイトル Transcriptional upregulation of HNF-1β by NF-κB in ovarian clear cell carcinoma modulates susceptibility to apoptosis through alteration in bcl-2 expression.
ジャーナル Lab Invest
Abstract Hepatocyte nuclear factor-1β (HNF-1β) is a transcriptional factor that has an important role in endometriosis-ovarian clear cell carcinoma (OCCC) sequence by modulating cell kinetics and glucose metabolism. However, little is known about the detailed molecular mechanisms that govern its regulation and function. Herein, we focus on upstream and downstream regulatory factors of HNF-1β in OCCCs. In clinical samples, HNF-1β expression was positively correlated with the active form of NF-κB/p65 in OCCCs, and closely linked with a low nuclear grade and non-solid architecture. In cell lines, transfection of p65 resulted in increased HNF-1β mRNA and protein expression in TOV-21G cells (OCCC cell line with endogenous HNF-1β expression), in line with activation of the promoter, probably through interacting with the basic transcriptional machinery. Suppression of endogenous HNF-1β expression by siRNA increased apoptosis in TOV-21G cells, while treatment of Hec251 cells (endometrial carcinoma cell line with extremely low endogenous HNF-1β expression) stably overexpressing exogenous HNF-1β with doxorubicin abrogated apoptosis of the cells, along with increased ratio of bcl-2 relative to bax. Moreover, overexpression of HNF-1β led to upregulation of bcl-2 expression at the transcriptional level in TOV-21G cells, which provided evidence for a positive correlation between HNF-1β and bcl-2 expression in OCCCs. These data, therefore, suggest that association between HNF-1β and NF-κB signaling may participate in cell survival by alteration of apoptotic events, particularly in mitochondria-mediated pathways, through upregulation of bcl-2 expression in OCCCs.
巻・号 95(8)
ページ 962-72
公開日 2015-8-1
DOI 10.1038/labinvest.2015.73
PII labinvest201573
PMID 26030369
MeSH Adenocarcinoma, Clear Cell / chemistry Adenocarcinoma, Clear Cell / metabolism* Adenocarcinoma, Clear Cell / pathology Adult Aged Apoptosis / genetics* Cell Proliferation / genetics Female Hepatocyte Nuclear Factor 1-beta / genetics* Hepatocyte Nuclear Factor 1-beta / metabolism Humans Immunohistochemistry Middle Aged NF-kappa B / genetics* NF-kappa B / metabolism Ovarian Cysts / chemistry Ovarian Cysts / metabolism Ovarian Cysts / pathology Ovarian Neoplasms / chemistry Ovarian Neoplasms / metabolism* Ovarian Neoplasms / pathology Ovary / chemistry Ovary / metabolism Ovary / pathology Proto-Oncogene Proteins c-bcl-2 / genetics* Proto-Oncogene Proteins c-bcl-2 / metabolism Up-Regulation / genetics
IF 4.197
引用数 15
WOS 分野 PATHOLOGY MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
遺伝子材料 pGL4-phHNF4A146 (RDB07534)