RRC ID 37635
著者 Ishibashi M, Nakayama K, Yeasmin S, Katagiri A, Iida K, Nakayama N, Miyazaki K.
タイトル Expression of a BTB/POZ protein, NAC1, is essential for the proliferation of normal cyclic endometrial glandular cells and is up-regulated by estrogen.
ジャーナル Clin Cancer Res
Abstract PURPOSE:The purpose of this study was to investigate the expression and localization of NAC1, a member of the BTB/POZ gene family in the human cyclic endometrium.
EXPERIMENTAL DESIGN:NAC1 expression in normal cyclic endometrium was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. To elucidate the molecular mechanisms of NAC1 expression in the normal endometrium endometrial carcinoma cell lines (Ishikawa, HHUA; ER+, PR+) and primary cultured normal endometria were tested in a sex steroid induction assay and a NAC1 knockdown assay using siRNA.
RESULTS:Expression of NAC1 in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases. Both NAC1 RNA and protein expression were up-regulated by treatment with 10 nmol/L 17beta-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells. The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1 gene knockdown inhibited cell growth and induced apoptosis in Ishikawa, HHUA, and normal endometria, all of which expressed NAC1. Furthermore, NAC1 siRNA significantly abrogated estrogen-driven cellular proliferation in Ishikawa, HHUA, and primary cultured normal endometrial cells, whereas the control siRNA had no effect on cell growth in any of these cells.
CONCLUSIONS:These findings suggest that NAC1 is functionally involved in E2-induced cell growth of the normal endometrial glandular cells. Because NAC1 is thought to have oncogenic potential, the current findings may provide new insight into the mechanism of estrogen induced endometrial carcinogenesis.
巻・号 15(3)
ページ 804-11
公開日 2009-2-1
DOI 10.1158/1078-0432.CCR-08-2134
PII 15/3/804
PMID 19188150
MeSH Cell Proliferation Cells, Cultured Endometrium / metabolism* Endometrium / physiology Estrogens / pharmacology Female Gene Expression Gene Silencing Humans Immunohistochemistry Menstrual Cycle / metabolism Neoplasm Proteins / physiology* Progesterone / pharmacology Repressor Proteins / physiology*
IF 10.107
引用数 12
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 HHUA(RCB0658)