Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial–mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone–dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts:

颗粒状样2（Grhl2）是调节细胞粘附基因的转录因子。Grhl2充当上皮-间质转化抑制物，并且是参与雌激素刺激的乳腺癌增殖的原癌基因。但是，其在卵巢激素依赖性乳腺导管发育过程中的表达仍然不清楚。我们在这里检查了正常和类固醇替代卵巢切除小鼠的乳腺中的Grhl2表达。在乳腺上皮细胞和肌上皮细胞核中均检测到Grhl2蛋白信号。青春期开始后，Grhl2阳性细胞核的比例和密度随着年龄的增长而增加，而在成熟的导管中检测到Grhl2阴性的上皮细胞。乳腺中的Claudin 3，claudin 4，claudin 7和E-cadherin基因表达上调，它们的表达与Grhl2基因表达高度相关。此外，与单独使用雌激素相比，通过雌激素和孕激素的联合治疗，Grhl2 mRNA表达和导管腔宽度显着增加。这些结果表明，Grhl2从导管发育的早期开始在腔上皮和肌上皮细胞中表达，从而控制细胞粘附分子的表达以建立功能性导管：