Crichton M B, Nichols J E, Zhao Y, Bulun S E, Simpson E R
Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA 75235-9051.
Mol Cell Endocrinol. 1996 Apr 19;118(1-2):215-20. doi: 10.1016/0303-7207(96)03761-6.
The expression of transcripts of cytokines of the interleukin-6 (IL-6) family has been examined in human breast tumors, breast cancer cell lines, and adipose stromal cells, by means of reverse transcription polymerase chain reaction amplification. Of the six breast tumor samples examined, all expressed transcripts encoding IL-6 and Leukemia Inhibitory Factor (LIF). Four of the samples also expressed transcripts for oncostatin M (OSM) and IL-11, and three expressed the IL-6 receptor. Adipose stromal cells expressed IL-6, IL-11 and LIF, but not the IL-6 receptor, consistent with previous conclusions that IL-6 activity in these cells required addition of IL-6 soluble receptor. In the case of T47D cells, expression of IL-11 protein was confirmed by immunotitration. Moreover, in these cells, expression of IL-11 transcripts was induced 3-fold by addition of estradiol to the culture medium. These results add credence to our previous proposal that breast cancer development is regulated in part by local autocrine and paracrine mechanisms via epithelial/mesenchymal interactions, in which estrogen produced by stromal cells surrounding the tumor acts to stimulate the production of growth factors and cytokines by the tumor cells. Some of these may act to stimulate further the growth and development of the tumor, while these or other factors may act on the surrounding mesenchymal cells in a paracrine fashion to stimulate aromatase expression in the presence of glucocorticoids. Thus, a positive feedback loop is established which leads to the development and growth of the tumor.
通过逆转录聚合酶链反应扩增技术，对人乳腺肿瘤、乳腺癌细胞系和脂肪基质细胞中白细胞介素-6（IL-6）家族细胞因子的转录本表达情况进行了检测。在所检测的6个乳腺肿瘤样本中，所有样本均表达编码IL-6和白血病抑制因子（LIF）的转录本。其中4个样本还表达抑瘤素M（OSM）和IL-11的转录本，3个样本表达IL-6受体。脂肪基质细胞表达IL-6、IL-11和LIF，但不表达IL-6受体，这与之前的结论一致，即这些细胞中的IL-6活性需要添加IL-6可溶性受体。在T47D细胞中，通过免疫滴定法证实了IL-11蛋白的表达。此外，在这些细胞中，向培养基中添加雌二醇可使IL-11转录本的表达增加3倍。这些结果进一步证明了我们之前的观点，即乳腺癌的发生发展部分受局部自分泌和旁分泌机制调控，通过上皮/间充质相互作用实现，其中肿瘤周围基质细胞产生的雌激素可刺激肿瘤细胞产生生长因子和细胞因子。其中一些因子可能进一步刺激肿瘤的生长和发展，而这些因子或其他因子可能以旁分泌方式作用于周围的间充质细胞，在糖皮质激素存在的情况下刺激芳香化酶的表达。因此，建立了一个正反馈回路，导致肿瘤的发生和生长。
