Journal
CELL CYCLE
Volume 11, Issue 19, Pages 3691-3700Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.21946
Keywords
estrogen; estrogen receptor alpha (ERA); circadian clock; PER2; BMAL1; breast epithelial cells; 3D acinar morphogenesis
Categories
Funding
- Department of Defense (DOD) [W81XWH0610657]
- Breast Cancer Coalition of Rochester
- Friends for an Earlier Test for Breast Cancer Foundation
- National Cancer Institute (NCI) [P30 CA016056]
- U.S. Department of Defense (DOD) [W81XWH0610657] Funding Source: U.S. Department of Defense (DOD)
Ask authors/readers for more resources
Altered estrogen receptor a (ERA) signaling and altered circadian rhythms are both features of breast cancer. By using a method to entrain circadian oscillations in human cultured cells, we recently reported that the expression of key clock genes oscillates in a circadian fashion in ERA-positive breast epithelial cells but not in breast cancer cells, regardless of their ERA status. Moreover, we reported that ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells. By using ERA-positive HME1 breast epithelial cells, which can be both entrained in vitro and can form mammary gland-like acinar structures in three-dimensional (3D) culture, first we identified a circuit encompassing ERA and an estrogen-regulated loop consisting of two circadian clock genes, PER2 and BMAL1. Further, we demonstrated that this estrogen-regulated circuit is necessary for breast epithelial acinar morphogenesis. Disruption of this circuit due to ERA-knockdown, negatively affects the estrogen-sustained circadian PER2-BMAL1 mechanism as well as the formation of 3D HME1 acini. Conversely, knockdown of either PER2 or BMAL1, by hampering the PER2-BMAL1 loop of the circadian clock, negatively affects ERA circadian oscillations and 3D breast acinar morphogenesis. To our knowledge, this study provides the first evidence of the implication of an ERA-circadian clock mechanism in the breast acinar morphogenetic process.
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