Abstract
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. 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. 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. 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.
Highlights
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
To examine the effect of E2 or P4 on NAC1 expression, estrogen receptors (ER)- and progesterone receptor – positive Ishikawa and HHUA endometrial cancer cells, and primary cultured cells established from normal endometria (EM-1) were cultured in the absence or presence of E2 or P4
To clarify whether NAC1 induction was mediated by ER signaling, HeLa cells that did not express the ER were used for the E2 induction assay
Summary
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. To elucidate the molecular mechanisms of NAC1expression 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 NAC1knockdown assay using siRNA. Results: Expression of NAC1in glandular cells was significantly higher in the early and mid proliferative phases than in the other menstrual phases Both NAC1RNA and protein expression were up-regulated by treatment with 10 nmol/L17h-Estradiol (E2) in Ishikawa, HHUA and primary cultured normal endometrial cells.The estrogen receptor antagonist ICI 182,780 significantly attenuated E2-induced NAC1 expression. NAC1siRNA 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. The purpose of this study was to investigate the expression and localization of NAC1 in the human endometrium at different phases of the menstrual cycle
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