Involvement of Akt, Ras and cell cycle regulators in the potential development of endometrial hyperplasia in women with polycystic ovarian syndrome.
Involvement of Akt, Ras and cell cycle regulators in the potential development of endometrial hyperplasia in women with polycystic ovarian syndrome.
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DOI：
10.1016/j.ygyno.2009.06.033
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发表时间：
2009-10
影响因子：
4.7
通讯作者：
Vega, M.
中科院分区：
文献类型：
--
作者：
Villavicencio, A.;Goyeneche, A.;Telleria, C.;Bacallao, K.;Gabler, F.;Fuentes, A.;Vega, M.
研究细胞周期调节因子CDK2、Cyclin E、p27和存活蛋白AKT和Ras在pcos相关子宫内膜（伴和不伴增生）中的丰度、定位和/或活性是否与非pcos子宫内膜不同。采用免疫组化和/或免疫印迹法检测9块正常子宫内膜（NE）、12块不伴有子宫内膜增生的PCOS患者子宫内膜（PCOSE）、7块伴有子宫内膜增生的PCOS患者子宫内膜（HPCOSE）和9块伴有子宫内膜增生的患者子宫内膜中CDK2、Cyclin E、p27、AKT和Ras的表达。CDK2的活性通过体外激酶试验进行评估。CDK2、Cyclin E和p27蛋白主要在实验组子宫内膜上皮细胞中表达。从组织样品中获得的总提取物中未观察到CDK2活性的变化。然而，与NE相比，上皮细胞中CDK2的核表达在PCOSE中略有升高，在HPCOSE中显著升高。PCOSE和HPCOSE的上皮细胞细胞质中p27的表达高于NE。此外，我们发现PCOS患者子宫内膜中Ser473-AKT磷酸化增加，Ras癌基因过度表达。PCOS与子宫内膜上皮细胞Ser473-AKT磷酸化升高、Ras表达升高、细胞质p27丰度升高和CDK2核丰度升高有关。这些生物学事件可能为多囊卵巢综合征患者的子宫内膜细胞退出受控制的细胞周期并在后期变得增生提供了机会。
To examine whether the abundance, localization, and/or activity of cell cycle regulators CDK2, Cyclin E, p27, and survival proteins AKT and Ras in PCOS-associated endometria (with and without hyperplasia) differ from non-PCOS endometria. The expression of CDK2, Cyclin E, p27, AKT and Ras was measured by immunohistochemistry and/or Western blot in 9 normal endometria (NE), 12 endometria from PCOS patients without endometrial hyperplasia (PCOSE), 7 endometria from PCOS women with endometrial hyperplasia (HPCOSE), and 9 endometria from patients with endometrial hyperplasia (HE). The activity of CDK2 was assessed by an in vitro kinase assay. CDK2, Cyclin E and p27 proteins were expressed mainly in the endometrial epithelial cells of the studied groups. No change in the activity of CDK2 was observed in total extracts obtained from the tissue samples. However, the nuclear expression of CDK2 in epithelial cells was slightly elevated in PCOSE and significantly increased in HPCOSE when compared to NE. Higher expression of p27 was detected in the cytoplasm of epithelial cells of PCOSE and HPCOSE when compared to NE. Also, we found an increment in Ser473-AKT phosphorylation and an over-expression of the Ras oncogene in endometria of patients with PCOS. The PCOS condition is associated with increased Ser473-AKT phosphorylation, elevated expression of Ras, increased cytoplasmic abundance of p27, and increased nuclear abundance of CDK2 in the endometrial epithelial cells. These biological events could potentially provide a chance for endometrial cells from PCOS patients to exit the controlled cell cycle and become hyperplastic at a later stage.
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DOI：
10.1016/j.jsbmb.2007.09.020
发表时间：
2008-02-01
影响因子：
4.1
作者：
Doll, A.;Abal, M.;Reventos, J.
通讯作者：
Reventos, J.
DOI：
10.1016/s1028-4559(08)60102-3
发表时间：
2007-03-01
影响因子：
2.1
作者：
Liu, Fu-Shing
通讯作者：
Liu, Fu-Shing
DOI：
10.1111/j.1525-1438.2006.00541.x
发表时间：
2006-05-01
影响因子：
4.8
作者：
Erkanli, S.;Kayaselcuk, F.;Demirhan, B.
通讯作者：
Demirhan, B.
影响因子：
4.3
作者：
Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.
影响因子：
82.9
作者：
Liang, J;Zubovitz, J;Slingerland, JM
通讯作者：
Slingerland, JM