Helftenbein G, Misseyanni A, Hagen G, Peter W, Slater E P, Wiehle R D, Suske G, Beato M
Institut für Molekularbiologie und Tumorforschung (IMT), Marburg, Federal Republic of Germany.
Ann N Y Acad Sci. 1991;622:69-79. doi: 10.1111/j.1749-6632.1991.tb37851.x.
To understand the molecular mechanism of endometrial differentiation we have initiated an analysis of the uteroglobin promoter. Uteroglobin is normally expressed in endometrial tissues under the control of ovarian hormones. In gene transfer experiments with the Ishikawa cell line, derived from a human endometrial adenocarcinoma, we have identified several regions in the promoter of the uteroglobin gene that are responsible for its endometrium-specific expression. To evaluate the generality of these findings, we have begun cloning the promoter regions of potential endometrial markers, including the rat, mouse, and human uteroglobin gene. In the rat, expression of the uteroglobin-like gene, CC10, is dominant in the lung but is also observed in the endometrium of progesterone treated animals. A comparison of the 5'-flanking sequence of the rat and rabbit uteroglobin gene resulted in the detection of similarities and differences that could explain their differential expression in vivo. To substantiate these findings we have established several cell lines from rat endometrium using murine retroviral vectors containing a positive selection marker and various viral oncogenes, such as SV40 large T antigen, adenovirus E1A, and Ha-ras. Cell lines immortalized by SV40 T-antigen were subsequently transformed with the Ha-ras oncogene. Several cell lines exhibit properties of epithelial endometrial cells. Two cell lines generated with a temperature sensitive mutant of the SV40 large T-antigen grow as transformed cells at the permissive temperature, but differentiate upon shifting to the non-permissive temperature. These rat endometrial cell lines should be useful for the analysis of endometrium-specific gene expression and as model systems for endometrial carcinoma.
为了解子宫内膜分化的分子机制，我们已开始对子宫珠蛋白启动子进行分析。子宫珠蛋白通常在卵巢激素的控制下于子宫内膜组织中表达。在用人子宫内膜腺癌来源的 Ishikawa 细胞系进行的基因转移实验中，我们已在子宫珠蛋白基因的启动子中鉴定出几个负责其子宫内膜特异性表达的区域。为评估这些发现的普遍性，我们已开始克隆潜在子宫内膜标志物的启动子区域，包括大鼠、小鼠和人类的子宫珠蛋白基因。在大鼠中，类子宫珠蛋白基因 CC10 的表达在肺中占主导地位，但在经孕酮处理的动物的子宫内膜中也可观察到。对大鼠和兔子宫珠蛋白基因的 5' 侧翼序列进行比较，发现了一些异同点，这些异同点可以解释它们在体内的差异表达。为证实这些发现，我们使用含有阳性选择标记和各种病毒癌基因（如 SV40 大 T 抗原、腺病毒 E1A 和 Ha-ras）的鼠逆转录病毒载体，从大鼠子宫内膜建立了几种细胞系。随后用 Ha-ras 癌基因转化由 SV40 T 抗原永生化的细胞系。几种细胞系表现出子宫内膜上皮细胞的特性。用 SV40 大 T 抗原的温度敏感突变体产生的两种细胞系在允许温度下以转化细胞的形式生长，但在转移到非允许温度时会发生分化。这些大鼠子宫内膜细胞系应有助于分析子宫内膜特异性基因表达，并可作为子宫内膜癌的模型系统。
