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- W4361960874 abstract "<div>Abstract<p><b>Purpose and experimental design:</b> Despite the therapeutic utility of progestin in invasive and preinvasive endometrial neoplasias, the molecular mechanisms through which it exerts inhibitory effects on endometrial epithelial growth are largely unknown. The aim of the study was to clarify the molecular mechanisms of progestin action to endometrial epithelial cells using originally established <i>in vitro</i> and <i>in vivo</i> treatment models for immortalized and transformed endometrial epithelial cell lines that express progesterone receptor.</p><p><b>Results:</b> In this model, progestin effectively inhibited the cell growth, inducing G0/G1 arrest rather than apoptosis without p21/WAF-1 induction. Using DNA microarray analysis, we identified 24 genes whose expression increased more than 10-fold on progestin treatment. Of these genes, we paid special attention to forkhead box transcription factor <i>FOXO1</i>, known as a key gene for endometrial decidualization. Progestin markedly induced <i>FOXO1</i> gene expression mainly in the nuclei <i>in vitro</i> and <i>in vivo</i>. This induction was not due to the canonical activation of FOXO1 via protein dephosphorylation but due to <i>FOXO1</i> promoter activation and mRNA induction. siRNA inhibition of <i>FOXO1</i> significantly attenuated the effects of progestin to inhibit endometrial epithelial cell growth. Disrupting Akt activity by the introduction of the dominant negative form of <i>Akt</i> increased nuclear FOXO1 accumulation and enhanced the effect of progestin.</p><p><b>Conclusion:</b> These findings suggest that <i>FOXO1</i> is a direct target of progestin, implicating novel molecular mechanisms of progestin to eradicate endometrial neoplasia. <i>Clin Cancer Res; 17(3); 525–37. ©2010 AACR</i>.</p></div>" @default.
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- W4361960874 date "2023-03-31" @default.
- W4361960874 modified "2023-10-18" @default.
- W4361960874 title "Data from Forkhead Transcription Factor FOXO1 is a Direct Target of Progestin to Inhibit Endometrial Epithelial Cell Growth" @default.
- W4361960874 doi "https://doi.org/10.1158/1078-0432.c.6519848" @default.
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