Transgenic mammary epithelial osteopontin (spp1) expression induces proliferation and alveologenesis.
Transgenic mammary epithelial osteopontin (spp1) expression induces proliferation and alveologenesis.
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DOI：
10.1177/1947601913496813
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发表时间：
2013-05-01
期刊：
影响因子：
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通讯作者：
Borowsky, Alexander D
中科院分区：
文献类型：
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作者：
Hubbard, Neil E;Chen, Qian J;Borowsky, Alexander D
骨桥蛋白（OPN）Spp 1参与乳腺的分化。我们设计小鼠在乳腺上皮中过表达OPN，并描述了改变的乳腺表型。FVB/NJ原核注射后繁殖了三个转基因（Tg）创始系FVB/N Tg（MMTV-Opn）（（1-3BOR））。与同窝对照相比，Tg-OPN小鼠的乳腺显示，在4周龄时，末端芽增大;在8周和12周时，管腔蛋白增加的导管更多且复杂;在16周时，小叶形成增加。哺乳期Tg-OPN乳腺表现出更快的小叶发育和哺乳期变化，断奶后腺体退化和退化较慢。Tg-OPN小鼠的类器官的离体小叶形成显著增加。免疫组织化学显示Tg-OPN乳腺中细胞质OPN蓄积和Ki-67阳性乳腺上皮细胞增加。OPN似乎传递乳腺上皮细胞的增殖刺激并改变发育和分化。这些OPN乳腺过表达小鼠提供了一种研究OPN在癌症进展中作用的方法。
Osteopontin (OPN) Spp1 is involved in differentiation of the mammary gland. We engineered mice to overexpress OPN in mammary epithelium and describe an altered mammary phenotype. Three transgenic (Tg) founder lines FVB/N Tg(MMTV-Opn)((1-3BOR)) were propagated after FVB/NJ pronuclear injections. Mammary glands from Tg-OPN mice compared to littermate controls showed, at 4 weeks of age, exaggerated terminal end buds; at 8 and 12 weeks, more numerous and complex ducts with increased luminal protein; and at 16 weeks, increased lobulogenesis. Lactational Tg-OPN mammary glands showed more rapid lobulogenesis and lactational changes with slower gland involution and regression following weaning. Ex vivo lobulogenesis was noticeably increased from organoids of Tg-OPN mice. Immunohistochemistry revealed cytoplasmic OPN accumulation and increased Ki-67 positive mammary epithelial cells in Tg-OPN mammary glands. OPN appears to convey a proliferative stimulus for mammary epithelial cells and alters development and differentiation. These OPN mammary overexpressing mice provide a means to study the role of OPN in cancer progression.