GPER-1 acts as a tumor suppressor in ovarian cancer.
GPER-1 acts as a tumor suppressor in ovarian cancer.
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DOI：
10.1186/1757-2215-6-51
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发表时间：
2013-07-13
影响因子：
4
通讯作者：
Ignatov A
中科院分区：
文献类型：
--
作者：
Ignatov T;Modl S;Thulig M;Weißenborn C;Treeck O;Ortmann O;Zenclussen A;Costa SD;Kalinski T;Ignatov A
已知新的膜结合型雌激素受体GPER - 1在乳腺癌细胞中起抑制作用，且在疾病进展过程中其表达降低。本研究旨在评估GPER - 1在卵巢癌中的表达及其与疾病进展的相关性，并在卵巢癌细胞中进行体外功能测试。
通过免疫组织化学方法分析了35例良性卵巢肿瘤、35例低度恶性潜能肿瘤和124例卵巢癌中的GPER - 1表达。将GPER - 1表达与前瞻性评估的卵巢癌患者的无病生存期相关联。我们还检测了卵巢癌细胞中的GPER - 1表达以及GPER - 1刺激对细胞生长的影响。
卵巢癌组织中的GPER - 1表达明显低于良性和低度恶性卵巢肿瘤。在83.1%的恶性肿瘤中观察到GPER - 1表达，且在早期癌症和组织学分化程度高的肿瘤中表达更高。GPER - 1表达与良好的临床结果相关。根据GPER - 1表达情况，2年无病生存期的差异显著，GPER - 1阴性病例为28.6%，GPER - 1阳性病例为59.2%（p = 0.002）。在SKOV - 3和OVCAR - 3卵巢癌细胞系中观察到GPER - 1表达。G - 1（一种选择性GPER - 1激动剂）通过抑制细胞周期在G2/M期的进展以及刺激半胱天冬酶依赖性凋亡，抑制了这两种细胞类型的增殖。G2/M期的阻滞与细胞周期蛋白B1和Cdc2的表达增加以及组蛋白3的磷酸化有关。
GPER - 1作为一种新的肿瘤抑制因子出现，对卵巢癌具有意想不到的治疗潜力。
It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells. GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer.
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影响因子：
3.8
作者：
Arias-Pulido, Hugo;Royce, Melanie;Gong, Yun;Joste, Nancy;Lomo, Lesley;Lee, Sang-Joon;Chaher, Nabila;Verschraegen, Claire;Lara, Juanita;Prossnitz, Eric R.;Cristofanilli, Massimo
通讯作者：
Cristofanilli, Massimo
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
11.2
作者：
Ariazi EA;Brailoiu E;Yerrum S;Shupp HA;Slifker MJ;Cunliffe HE;Black MA;Donato AL;Arterburn JB;Oprea TI;Prossnitz ER;Dun NJ;Jordan VC
通讯作者：
Jordan VC
DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.3
作者：
Ignatov, A.;Robert, J.;Schaller, H. C.
通讯作者：
Schaller, H. C.