The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer.
The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer.
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DOI：
10.1186/1757-2215-5-9
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发表时间：
2012-03-18
影响因子：
4
通讯作者：
Casslén B
中科院分区：
文献类型：
--
作者：
Kolkova Z;Casslén V;Henic E;Ahmadi S;Ehinger A;Jirström K;Casslén B
尽管卵巢肿瘤通常不被认为是雌激素敏感的，雌激素仍然可能对卵巢肿瘤的进展产生影响。最近发现的跨膜雌激素受体GPER参与快速雌激素信号传导。此外，它结合具有激动作用的选择性雌激素受体调节剂，这可以解释他莫昔芬的争议。应用实时荧光定量PCR（qPCR）检测了42例卵巢肿瘤组织和7株卵巢癌细胞株中GPER mRNA的表达。比较ERα和ERβ mRNA的表达。用免疫印迹法对40例卵巢肿瘤组织中GPER蛋白进行半定量分析，并用免疫组化法（IHC）分析其组织分布。此外，在150例原发性恶性卵巢肿瘤的组织微阵列（TMA）中评价了IHC。所有肿瘤样品均含有GPER mRNA。GPER mRNA在良、恶性肿瘤中的含量无明显差异，但1/3的恶性肿瘤组织中GPER mRNA过表达。ERα mRNA在恶性肿瘤中的含量高于良性肿瘤，ERβ mRNA在良性肿瘤中的含量高于恶性肿瘤。GPER mRNA在所有7个卵巢癌细胞系中均被检测到，其中TOV 21 G和TOV 112 D细胞中的GPER mRNA水平最高。ERβ mRNA表达模式相似。Western blot结果显示GPER蛋白在所有肿瘤组织中均有表达。半定量分析显示，良性和恶性肿瘤之间没有差异，但约三分之一的恶性肿瘤样本过表达GPER蛋白。GPER染色主要定位于上皮细胞。在TMA研究中，我们发现GPER染色与临床分期、组织学分级或患者生存率之间无相关性。GPER mRNA和GPER蛋白在卵巢良、恶性肿瘤组织中均有表达。约三分之一的恶性肿瘤同时过表达GPER mRNA和蛋白。然而，这与组织学或临床参数以及患者存活率均不相关。
Even though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies. GPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ERα and ERβ mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In addition, IHC was evaluated in a tissue microarray (TMA) of 150 primary malignant ovarian tumors. All tumor samples contained GPER mRNA. The content of mRNA was not different between benign and malignant tumors, but one third of malignant samples over-expressed GPER mRNA. The content of ERα mRNA was higher in malignant than in benign tumors, whereas ERβ mRNA was higher in benign than in malignant tumors. GPER mRNA was detected in all seven ovarian cancer cell lines with highest levels in TOV21G and TOV112D cells. Similar expression pattern was seen for ERβ mRNA. Western blot demonstrated GPER protein in all tumor samples. Semi-quantification showed no difference between benign and malignant tumors, but about one third of malignant samples over-expressed GPER protein. GPER staining was localized mainly in epithelial cells. In the TMA study we found no correlation between GPER staining and clinical stage, histological grade or patient survival. GPER mRNA as well as GPER protein is present in both benign and malignant ovarian tumor tissue. About one third of malignant tumors over-expressed both GPER mRNA and protein. This, however, correlated neither with histological or clinical parameters nor with patient survival.
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