Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor.
Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor.
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DOI：
10.1084/jem.20031233
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发表时间：
2003-12-15
期刊：
影响因子：
--
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Yeh S;Hu YC;Wang PH;Xie C;Xu Q;Tsai MY;Dong Z;Wang RS;Lee TH;Chang C
雄激素受体（AR）缺乏（AR-/-）的雌性小鼠的表型分析表明，乳腺发育迟缓，青春期前阶段导管分支减少，末端芽中帽细胞减少，成年雌性小叶肺泡发育减少，泌乳腺中产奶肺泡减少。AR-/-乳腺的发育缺陷涉及胰岛素样生长因子I-胰岛素样生长因子I受体和有丝分裂原活化蛋白激酶（MAPK）信号以及雌激素受体（ER）活性的缺陷。在AR −/− MCF 7乳腺癌细胞中也发现了类似的生长迟缓和生长因子介导的Ras/Raf/MAPK级联反应和ER信号传导缺陷。恢复分析表明，AR NH 2-末端/DNA结合域，而不是配体结合域，是必需的正常MAPK功能在MCF 7细胞，和AR突变体（R608 K），发现在男性乳腺癌，与MAPK的过度激活。总之，我们的数据提供了第一个体内证据，表明AR介导的MAPK和ER激活可能在乳腺发育和MCF 7乳腺癌细胞增殖中发挥重要作用。
Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR −/−) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR −/− mammary glands involves the defects of insulin-like growth factor I–insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor–mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR −/− MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation.
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影响因子：
7.8
作者：
Niemann, C;Brinkmann, V;Spitzer, E;Hartmann, G;Sachs, M;Naundorf, H;Birchmeier, W
通讯作者：
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影响因子：
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3.5
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通讯作者：
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影响因子：
11.8
作者：
Brisken, C;Ayyannan, A;Heineman, A
通讯作者：
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影响因子：
11.4
作者：
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通讯作者：
Auricchio, F