Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Development. 2011 Dec;138(23):5247-56. doi: 10.1242/dev.069203.
The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.
ID 家族的螺旋-环-螺旋蛋白在许多不同的发育途径中调节细胞增殖和分化，但 ID4 在乳腺发育中的功能尚不清楚。我们报告说，小鼠 Id4 表达于帽细胞、基底细胞和腔上皮细胞亚群中，其靶向缺失会损害导管扩张和分支形态发生，以及雌激素和/或孕激素诱导的细胞增殖。我们发现，p38MAPK 在 Id4 缺失的乳腺细胞中被激活。siRNA 介导的转化乳腺细胞中 Id4 敲低后，p38MAPK 也被激活。这种 p38MAPK 的激活对于 Id4 缺失的乳腺中增殖减少和凋亡增加是必需的。因此，ID4 通过抑制 p38MAPK 的活性来促进乳腺发育。
