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Our study using a mouse model with <jats:italic>Tsc1<\/jats:italic> conditionally knockout in mammary epithelium showed that <jats:italic>Tsc1<\/jats:italic> deficiency impaired mammary development. Phosphorylated S6 was up-regulated in <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mammary epithelium. The mTORC1 inhibitor rapamycin restored the development of <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mammary glands whereas suppressed the development of <jats:italic>Tsc1<\/jats:italic><jats:sup><jats:italic>wt\/wt<\/jats:italic><\/jats:sup> mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Phosphorylated PDK1 and AKT, nuclear ER\u03b1, nuclear IRS-1, SGK3 and cell cycle regulators such as Cyclin D1, Cyclin E, CDK2, CDK4 and their target pRB were all apparently down-regulated in <jats:italic>Tsc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mammary glands, which could be reversed by rapamycin, suggesting that suppression of AKT by hyperactivation of mTORC1, inhibition on nuclear ER\u03b1 signaling and down-regulation of cell-cycle-driving proteins play important roles in the retarded mammary development induced by <jats:italic>Tsc1<\/jats:italic> deletion. This study demonstrated for the first time the <jats:italic>in vivo<\/jats:italic> role of <jats:italic>Tsc1<\/jats:italic> in pubertal mammary development of mice and revealed that loss of <jats:italic>Tsc1<\/jats:italic> does not necessarily lead to tissue hyperplasia.<\/jats:p>","DOI":"10.1038\/srep19587","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T10:01:24Z","timestamp":1453456884000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tsc1 deficiency impairs mammary development in mice by suppression of AKT, nuclear ER\u03b1 and cell-cycle-driving proteins"],"prefix":"10.1038","volume":"6","author":[{"given":"Zhenqi","family":"Qin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenshu","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuilan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchun","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiasong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,22]]},"reference":[{"key":"BFsrep19587_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1749-6632.2009.05117.x","volume":"1184","author":"KA Orlova","year":"2010","unstructured":"Orlova, K. 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