Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction
Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction
复制标题
DOI：
10.1677/erc-07-0227
复制
发表时间：
2008-06-01
影响因子：
3.9
通讯作者：
Hayashi, Shin-ichi
中科院分区：
文献类型：
--
作者：
Matsumoto, Mitsuyo;Yamaguchi, Yuri;Hayashi, Shin-ichi
雌激素通路在人子宫内膜癌（EC）的病因学中起着重要作用。我们研究了肿瘤微环境中的雌激素生物合成是否促进了子宫内膜癌。为了研究基质细胞对EC中雌激素信号传导的贡献，我们使用了稳定转染雌激素反应元件（ERE）的报告细胞，该元件与不稳定的绿色荧光蛋白（GFP）基因融合。在这个系统中，来自几个患者的子宫内膜癌间质细胞不同程度地激活了癌细胞的ERE。当添加芳香化酶底物睾酮时，GFP表达水平升高。芳香化酶抑制剂（Als）不同程度地抑制了这种效果，尽管不同患者对Als的反应不同。这些结果表明，在子宫内膜癌基质细胞中，GFP的表达是由芳香化酶合成的雌激素驱动的。在第二个实验中，我们构建了一个与上述报告细胞结构相同的腺病毒报告载体，并在15个EC标本的原代培养癌细胞中观察内源性ERE活性。GFP的表达水平在不同的病例中有所不同，在大多数原发组织中，ERE的活性被一种纯抗雌激素——氟维司酮强烈抑制。有趣的是，少数子宫内膜癌的原发组织显示出独立于雌激素- er途径的ERE活性。这些结果提示，Al可能对EC有一定的治疗价值；然而，激素微环境必须在开始治疗之前进行评估。
The estrogen pathway plays an important role in the etiology of human endometrial carcinoma (EC). We examined whether estrogen biosynthesis in the tumor microenvironment promotes endometrial cancer. To examine the contribution of stromal cells to estrogen signaling in EC, we used reporter cells stably transfected with the estrogen response element (ERE) fused to the destabilized green fluorescent protein (GFP) gene. In this system, the endometrial cancer stromal cells from several patients activated the ERE of cancer cells to a variable extent. The GFP expression level increased when testosterone, a substrate for aromatase, was added. The effect was variably inhibited by aromatase inhibitors (Als), although the response to Als varied among patients. These results suggest that GFP expression is driven by estrogen synthesized by aromatase in the endometrial cancer stromal cells. In a second experiment, we constructed an adenovirus reporter vector containing the same construct as the reporter cells described above, and visualized endogenous ERE activity in primary culture cancer cells from 15 EC specimens. The GFP expression levels varied among the cases, and in most primary tissues, ERE activities were strongly inhibited by a pure anti-estrogen, fulvestrant. Interestingly, a minority of primary tissues in endometrial cancer showed ERE activity independent of the estrogen-ER pathway. These results suggest that Al may have some therapeutic value in EC; however, the hormonal microenvironment must be assessed prior to initiating therapy.