Role of the androgen receptor in human breast cancer
Role of the androgen receptor in human breast cancer
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DOI：
10.1023/a:1018730519839
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发表时间：
1998-01-01
影响因子：
2.5
通讯作者：
Tilley, WD
中科院分区：
文献类型：
--
作者：
Birrell, SN;Hall, RE;Tilley, WD
虽然雄激素受体(AR)(3)在人类乳腺肿瘤中经常与雌激素受体(ER)和孕激素受体(PR)共表达，但它在乳腺癌中的作用尚不清楚。雄激素在人类乳腺癌细胞系中的特定生长刺激和抑制作用已被描述。雄激素发挥这些相反的生长效应的机制尚不清楚。治疗晚期乳腺癌常用的二线疗法是大剂量醋酸甲羟孕酮(MPA)。虽然甲孕酮，一种人工合成的孕激素，被认为只通过PR起作用，但在服用甲孕酮的女性中观察到的雄激素副作用表明，它的作用也可能部分通过AR调节。为了支持这一假说，放射配基结合法测量的乳腺癌AR水平与三苯氧胺治疗失败后对甲孕酮治疗的有效时间相关。最近的数据表明，乳腺癌中存在结构改变的AR可能是其中一些病例对甲孕酮无反应的原因。有必要进一步研究AR介导的通路在调节乳腺肿瘤生长中的作用。特别是，雄激素调节基因的识别可能会为乳腺癌的激素治疗带来新的可能性。
Although the androgen receptor (AR)(3) is often co-expressed with the estrogen receptor (ER) and progesterone receptor (PR) in human breast tumors, its role in breast cancer is poorly understood. Specific growth stimulatory and inhibitory actions of androgens have been described in human breast cancer cell lines. The mechanisms by which androgens exert these contrasting growth effects are unknown. A commonly utilized second line therapy for the treatment of advanced breast cancer is high dose medroxyprogesterone acetate (MPA). Although MPA, a synthetic progestin, was thought to act exclusively through the PR, the androgenic side-effects observed in women taking MPA suggest that its action may also be mediated in part by the AR. In support of this hypothesis, the level of AR measured by radioligand binding in primary breast tumors was correlated with the duration of response to MPA treatment following failure of tamoxifen therapy. Recent data suggest that the presence of structurally altered AR in breast cancers may account for unresponsiveness to MPA in some of these cases. Further studies are warranted to determine the role of AR mediated pathways in regulating breast tumor growth. In particular, identification of androgen-regulated genes may lead to new possibilities for the hormonal treatment of breast cancer.