Constitutive Overexpression of Id-1 in Mammary Glands of Transgenic Mice Results in Precocious and Increased Formation of Terminal End Buds, Enhanced Alveologenesis, Delayed Involution
- Authors
- Shin, Dong-Hui; Jang, Si-Hyong; Kang, Byeong-Cheol; Kim, Hyun-Jun; Oh, Seung Hyun; Kong, Gu
- Issue Date
- May-2011
- Publisher
- WILEY
- Citation
- JOURNAL OF CELLULAR PHYSIOLOGY, v.226, no.5, pp.1340 - 1352
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELLULAR PHYSIOLOGY
- Volume
- 226
- Number
- 5
- Start Page
- 1340
- End Page
- 1352
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/168523
- DOI
- 10.1002/jcp.22462
- ISSN
- 0021-9541
- Abstract
- Inhibitor of differentiation-1 (Id-1) has been shown to play an essential role in cell proliferation, invasion, migration, and anti-apoptosis. However, the effect of Id-1 in mammary gland development remains unknown. Here, we generated MMTV-Id-1 transgenic mice to study the role of Id-1 in mammary gland development. In virgin mice, Id-1 overexpression led to precocious development and delayed regression of terminal end buds (TEBs) compared with wild-type mice. The number of BrdU-positive cells and the expression of Wnt signaling molecules, beta-catenin and cyclin D1, which regulate ductal extension and TEB formation in virgin, were statistically higher in Id-1 transgenic mice than in wild-type mice. Id-1 also had an effect on the formation and proliferation of lobuloalveolar structures during early and mid-pregnancy. Id-1 transgenic mice had more lobulated and prominent alveolar budding than wild-type mice and had significantly greater counts of lobuloalveolar structures in early pregnancy. The expression of BrdU, beta-catenin, and cyclin D1 was also predominantly increased in Id-1 transgenic mice. Moreover, Id-1 transgenic mice showed delayed involution. Id-1 regulated the expression levels of anti-apoptotic Bcl-2 and pro-apoptotic Bax, and resulted in delay of apoptotic peak during postlactational involution. We also found that Id-1 was able to modulate expression of the regulators of Wnt/beta-catenin signaling such as phospho-Akt, BMP2, FGF3, and RAR-beta in tubuloalveolar development of mammary glands. Taken together, our results suggest that Id-1 plays a pivotal role in mammary gland development through Wnt signaling-mediated acceleration of precocity and alveologenesis and Bcl-2 family members-mediated delay of involution. J. Cell. Physiol. 226: 1340-1352, 2011.
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