Antiandrogens were originally developed as therapeutic agents for prostate cancer but are also expected to be effective for breast cancer. However, the role of androgen signaling in breast cancer has long been controversial due to the limited number of experimental models. Our study aimed to comprehensively investigate the efficacy of antiandrogens on breast cancer. In the present study, a total of 18 breast cancer cell lines were treated with the agonist or antagonists of the androgen receptor (AR). Among the 18 cell lines tested, only T-47D cells proliferated in an androgen-dependent manner, while the other cell lines were almost irresponsive to AR stimulation. On the other hand, treatment with AR antagonists at relatively high doses suppressed the proliferation of not only T-47D cells but also some other cell lines including AR-low/negative cells. In addition, expression of the full-length AR and constitutively active AR splice variants, AR-V7 and AR^V567es, was not correlated with sensitivity to AR antagonists. These data suggest that the antiproliferative effect of AR antagonists is AR-independent in some cases. Consistently, proliferation of AR-knockout BT-549 cells was inhibited by AR antagonists. Identification of biomarkers would be necessary to determine which breast cancer patients will benefit from these drugs.

中文翻译：

---

多种乳腺癌细胞系抗雄激素反应性分析

抗雄激素最初是作为前列腺癌的治疗剂而开发的，但预计也对乳腺癌有效。然而，由于实验模型数量有限，雄激素信号在乳腺癌中的作用长期以来一直存在争议。我们的研究旨在全面研究抗雄激素对乳腺癌的疗效。在本研究中，总共用雄激素受体（AR）激动剂或拮抗剂处理了 18 种乳腺癌细胞系。在测试的18个细胞系中，只有T-47D细胞以雄激素依赖性方式增殖，而其他细胞系对AR刺激几乎没有反应。另一方面，相对高剂量的AR拮抗剂治疗不仅抑制了T-47D细胞的增殖，而且抑制了包括AR低/阴性细胞在内的一些其他细胞系的增殖。此外，全长AR和组成型活性AR剪接变体AR-V7和AR ^V567es的表达与对AR拮抗剂的敏感性不相关。这些数据表明，AR拮抗剂的抗增殖作用在某些情况下是不依赖于AR的。一致地，AR 敲除的 BT-549 细胞的增殖受到 AR 拮抗剂的抑制。需要鉴定生物标志物来确定哪些乳腺癌患者将从这些药物中受益。