期刊
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
卷 69, 期 6, 页码 373-388出版社
SAGE PUBLICATIONS LTD
DOI: 10.1369/00221554211013715
关键词
claudin; E-cadherin; estrogen; Grainyhead-like 2; mammary gland; ovariectomy; postnatal development; progesterone
类别
资金
- KAKENHI grant [19H03116]
- Grants-in-Aid for Scientific Research [19H03116] Funding Source: KAKEN
Grhl2 is expressed in luminal epithelial and myoepithelial cells during early ductal development in the mammary gland, controlling the expression of cell adhesion molecules to establish functional ducts.
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:
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