Horvath G, Fernö M, Baldetorp B, Cameron R, Ranstam J
Department of Oncology, University Hospital, Lund, Sweden.
In Vivo. 1991 Jul-Aug;5(4):401-6.
To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.
为研究雌激素可利用性对生长模式以及其他肿瘤特征（如雌激素受体（ER）和孕激素受体（PgR）含量及组织病理学）的重要性，我们使用了一种人肿瘤-裸鼠模型，其中将一株ER和PgR阳性且对雌二醇敏感（受刺激）的人子宫内膜腺癌在雌性（未切除卵巢）裸鼠体内进行异种移植并连续传代一年。将该肿瘤的组织块移植到切除卵巢的裸鼠体内，随机分为两组，一组接受雌二醇治疗，另一组不接受雌二醇治疗（准备阶段）。四周后，将这两组的组织块再次移植到切除卵巢的裸鼠体内，每组再随机分为两个亚组，一个亚组接受雌二醇治疗，另一个亚组不接受雌二醇治疗（实验阶段）。在实验阶段测量肿瘤生长情况，而在实验阶段结束后分析ER和PgR含量以及组织病理学情况。我们的研究结果表明，即使在雌二醇缺乏的条件下短期生长也会引发诸如类固醇受体含量降低、肿瘤分化程度降低以及肿瘤生长增强趋势等渐进性变化。另一方面，富含雌二醇的条件会增强同一肿瘤细胞系中的ER激活、PgR诱导和肿瘤分化。因此，肿瘤生长所处的雌激素环境可能是肿瘤进展的关键决定因素。
