乳腺癌组织中孕激素受体与雌激素受体DNA结合功能关系的研究

Progesterone Receptor and Its Correlation with DNA-bindingFunction of Estrogen Receptor in Human Breast Cancer

目的：观察３６ 例（Ｅ２ ＋ ） 乳腺癌患者组织ＰＲ 和ＥＲ ＤＮＡ 结合功能的关系，进而探讨（Ｅ２ ＋ ／ＰＲ＋ ） 表型内分泌治疗无反应的分子机制。方法：用激素结合法和迁移率改变法。结果：１） 用含有ＥＲ 的ＭＣＦ－ ７ 细胞株作为阳性对照，２２ ℃Ｍｇ２ ＋ 存在条件下，迁移率改变法中ＥＲ－ ＥＲＥ 复合物的形成是激素依赖性的，证实了ＥＲ－ ＥＲＥ 复合物的特性。２） 激素结合法和迁移率改变法检测结果显示，３６ 例（Ｅ２ ＋ ） 乳腺癌中有２５ 例相一致，其中两种方法都是阳性者（ＰＲ＋ ／ＥＲＥ＋ ）１７ 例，都是阴性者（ＰＲ－ ／ＥＲＥ－ ）８ 例。３ 例肿瘤，激素结合法阳性而迁移率改变法阴性（ＰＲ＋ ／ＥＲＥ－ ） 。８ 例肿瘤，激素结合法阴性而迁移率改变法阳性（ＰＲ－ ／ＥＲＥ＋ ） 。结论：乳腺癌组织中依赖ＥＲ 的ＰＲ 表达还有其它途径（ＰＲ＋ ／ＥＲＥ－ ） ，且ＰＲ 阴性不能表示ＥＲ ＤＮＡ 结合功能状态有缺陷（ＰＲ－ ／ＥＲＥ＋ ） ，利用ＰＲ 评估ＥＲ ＤＮＡ 结合功能状态以指导乳腺癌的内分泌治疗存在约３０ ％ （１１／３６） 的误差率。因此，传统的激素结合法检测结果（Ｅ２ 、ＰＲ） 同迁移率改变法检测结果（ＥＲＥ） 相结合，能更准确地反应ＥＲ

Aim: To study the relationship between progesterone receptor (PR) and estrogen receptor (ER) DNA binding domain function in 36 breast cancers selected by testing E2 using hormone binding assay aiming to discuss the molecule mechanism of nonresponsiveness to endocrine therapy. Methods: Hormone binding assay and gel mobility shift assay were used. Results: 1)Using the ER-containing human breast cancer line MCF-7 as a positive control, we performed the mobility shift assay at 22℃in the presence of Mg2+to characterize the ER-ERE complex and found that the formation of ER-ERE complexes was estrogene-dependent. 2) Correlation of the mobility shift assay with the (PR )hormone-binding assay showed coincident with in 25 of the 36 tumors. Both assays were positive (PR+/ERE+) in 17 cases and both were negative in 8 cases. In 3 tumors, the hormone-binding assay was positive and the mobility shift assay negative (PR+/ERE-). In 8 cancers, the hormone-binding assay was negative and the mobility shift assay positive (PR-/ERE+). Conclusion: There is another pathway in the ER-dependent expression of PR in breast cancers and it is shown that PR(-) does not represent the defectiveness of ER DNA binding domain function, so there exist an 30% (11 / 36) error rate in the endocrine therapy according to PR estimation of the ER DNA binding domain function. Therefore, combination of detecting ERE (by the mobility shift assay) and PR (by hormone binding assay) could further truly determine the ER DNA binding domain function which could provide even more credible supports for postoperative aid endocrine therapy for breast cancers.