The AP-1 transcription factor regulates postnatal mammary gland development.
The AP-1 transcription factor regulates postnatal mammary gland development.
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DOI：
10.1016/j.ydbio.2006.03.042
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发表时间：
2006-07
影响因子：
2.7
通讯作者：
Q. Shen;Yun Zhang;I. Uray;Jamal L Hill;Heetae Kim;Chunhua Lu;M. Young;E. Gunther;S. Hilsenbeck-S.
中科院分区：
文献类型：
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作者：
Q. Shen;Yun Zhang;I. Uray;Jamal L Hill;Heetae Kim;Chunhua Lu;M. Young;E. Gunther;S. Hilsenbeck-S.
AP-1转录因子被多种生长因子激活，这些生长因子是乳腺细胞增殖的关键调节因子。我们以前证明，AP-1阻断抑制乳腺癌细胞的生长在体外。然而，AP-1在正常乳腺发育中的特定作用尚未研究。使用双转基因小鼠表达诱导型AP-1抑制剂（Tam67），我们发现AP-1因子调节乳腺上皮细胞的出生后增殖。在成年、青春期前、青春期和乳腺刺激的乳腺中，AP-1阻断后乳腺上皮增殖显著减少。在青春期小鼠中，乳腺细胞增殖大大减少，并且增殖的细胞不能表达Tam67。我们还观察到结构变化，如抑制分支和出芽，减少腺体树的大小，并减少脂肪垫占用后，AP-1封锁发展中的乳腺。我们进一步证明，Tam67抑制AP-1依赖性基因（TIMP-1，波形蛋白，Fra-1和纤连蛋白）和AP-1依赖性生长调节基因（细胞周期蛋白D1和c-myc）在AP-1阻断乳腺的表达。因此，我们得出结论，AP-1因子是出生后乳腺生长发育的关键调节因子。
The AP-1 transcription factor is activated by multiple growth factors that are critical regulators of breast cell proliferation. We previously demonstrated that AP-1 blockade inhibits breast cancer cell growth in vitro. Yet a specific role of AP-1 in normal mammary gland development has not been studied. Using a bi-transgenic mouse expressing an inducible AP-1 inhibitor (Tam67), we found that the AP-1 factor regulates postnatal proliferation of mammary epithelial cells. Mammary epithelial proliferation was significantly reduced after AP-1 blockade in adult, prepubertal, pubertal, and hormone-stimulated mammary glands. In pubertal mice, mammary cell proliferation was greatly reduced, and the cells that did proliferate failed to express Tam67. We also observed structural changes such as suppressed branching and budding, reduced gland tree size, and less fat pad occupancy in developing mammary glands after AP-1 blockade. We further demonstrated that Tam67 suppressed the expression of AP-1-dependent genes (TIMP-1, vimentin, Fra-1, and fibronectin) and the AP-1-dependent growth regulatory genes (cyclin D1 and c-myc) in AP-1-blocked mammary glands. We therefore conclude that AP-1 factor is a pivotal regulator of postnatal mammary gland growth and development.