Journal
DEVELOPMENTAL BIOLOGY
Volume 328, Issue 1, Pages 127-139Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2009.01.019
Keywords
Receptor Activator of Nuclear Factor-kappa B; Ligand (RANKL); Progesterone receptor; Prolactin; Transgenic; Mammary gland; Salivary gland; Morphogenesis; Tumorigenesis
Categories
Funding
- National Institutes of Health and private foundation [HD-042311, CA-077530]
- Susan G. Komen Breast Cancer Foundation [BCTR-0503763]
Ask authors/readers for more resources
Receptor of Activated NF-kappa B Ligand (RANKL) is implicated as one of a number of effector molecules that mediate progesterone and prolactin signaling in the murine mammary epithelium. Using a mouse transgenic approach, we demonstrate that installation of the RANKL signaling axis into the mammary epithelium results in precocious ductal side-branching and alveologenesis in the virgin animal. These morphological changes occur due to RANKL-induced mammary epithelial proliferation, which is accompanied by increases in expression of activated NF-kappa B and cyclin D1. With age, prolonged RANKL exposure elicits limited mammary epithelial hyperplasia. While these transgenics exhibit RANKL-induced salivary gland adenocarcinomas, palpable mammary tumors are not observed due to RANKL-suppression of its own signaling receptor (RANK) in the mammary epithelium. Together, these studies reveal not only that the RANKL signaling axis can program many of the normal epithelial changes attributed to progesterone and prolactin action in the normal mammary gland during early pregnancy, but Underscore the necessity for tight control of this signaling molecule to avoid unwarranted developmental changes that Could lead to mammary hyperplasia in later life. (C) 2009 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available