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:

Grainyhead-like 2 (Grhl2) 是一种调节细胞粘附基因的转录因子。Grhl2 作为上皮-间质转化抑制因子，是一种参与雌激素刺激的乳腺癌增殖的原癌基因。然而，它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去卵巢小鼠乳腺中的 Grhl2 表达。在乳腺腔上皮和肌上皮细胞核中均检测到 Grhl2 蛋白信号。Grhl2阳性细胞核的比例和密度在青春期开始后增加并随着年龄的增长而增加，而在成熟导管中检测到Grhl2阴性上皮细胞。Claudin 3、claudin 4、claudin 7 和 E-cadherin 基因在乳腺中的表达上调，并且它们的表达与Grhl2基因表达高度相关。此外，与单独使用雌激素相比，雌激素和孕激素联合治疗显着增加了 Grhl2 mRNA 表达和导管管腔宽度。这些结果表明，Grhl2 在导管发育早期就在管腔上皮和肌上皮细胞中表达，控制细胞粘附分子的表达以建立功能性导管：