【摘 要】
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Snail plays an important role in metastasis of ovarian cancer;our previous works confirmed that Snail expression correlated with the stage of ovarian cancer.To further illustrate the mechanisms of Sna
【机 构】
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Ob & Gyn Hospital of Fudan University China
【出 处】
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BIT`s 1st International Congress of Gynaecology and Obstetri
论文部分内容阅读
Snail plays an important role in metastasis of ovarian cancer;our previous works confirmed that Snail expression correlated with the stage of ovarian cancer.To further illustrate the mechanisms of Snail regulation in ovarian cancer, we performed the Reverse Phase Protein Assay (RPPA) using the SKOv3-Snail inducible cell line.RPPA analysis revealed that Dnmt1, the maintenance DNA methylation enzyme, was extremely high in Snail induced cells compared to the control.Snail-Dnmtl correlation was validated by Western blot in SKOv3-Snail and HO8910PM-Snail inducible cells.Most interesting finding is that compare to no-induced cells, the protein level of Dnmt1 was enhanced in the cytoplasm after Snail overexpressed, while there is no change in nucleus both in Snail-induced cells and its control.We therefore investigated whether Dnmt1 expression was associated with Snail, Dnmt1 was examined in an ovarian tissue array by immunohistochemistry,it shows that the expression of Dnmt1 was extremely higher in metastasis tumor compared with its primary tumor.Most intriguingly, we observed that Dnmt1 was mainly localized in the nucleus of primary tumors;whereas it exhibited a higher level in both nucleus and cytoplasm of metastasis lesions, as we know, sequestration of Dnmt1 in the cytoplasm may result global DNA hypomethylation.To understand the epigenetic alteration by Snail, SKOv3-Snail inducible cells were used to perform methylation array analysis.Chip analysis found methylation level of more than 40 genes were decreased after Snail induction, these genes were involved in cell transcription and adhesion.Our results inferred that Snail might regulate gene methylation through sequestering Dnmt1 in cytoplasm.
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