期刊
GENES & DEVELOPMENT
卷 24, 期 9, 页码 947-956出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1896810
关键词
14-3-3 sigma; ErbB2; conditional knockout; epithelial polarity
资金
- DoD [W81XWH-06-1-0700]
- CIHR [CIHR MOP-10594]
The loss of epithelial polarity is thought to play an important role during mammary tumor progression. Using a unique transgenic mouse model of ErbB2-induced mammary tumorigenesis, we demonstrated previously that amplification of ErbB2 is frequently accompanied by loss of the 14-3-3 sigma gene. Here, we demonstrate that ectopic expression of 14-3-3 sigma results in restoration of epithelial polarity in ErbB2-transformed mammary tumor cells. We further demonstrate that targeted deletion of 14-3-3 sigma within primary mammary epithelial cells increases their proliferative capacity and adversely affects their ability to form polarized structures. Finally, we show that 14-3-3 sigma can specifically form complexes with Par3, a protein that is essential for the maintenance of a polarized epithelial state. Taken together, these observations suggest that 14-3-3 sigma plays a critical role in retaining epithelial polarity.
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