A novel role for 14-3-3sigma in regulating epithelial cell polarity.
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 14-3-3sigma gene. Here, we demonstrate that ectopic expression of 14-3-3sigma results in restoration of epithelial polarity in ErbB2-transformed mammary tumor cells. We further demonstrate that targeted deletion of 14-3-3sigma within primary mammary epithelial cells increases their proliferative capacity and adversely affects their ability to form polarized structures. Finally, we show that 14-3-3sigma 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 14-3-3sigma plays a critical role in retaining epithelial polarity.
Ling
Chen
C
Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada.
Zuo
Dongmei
D
Xue
Bin
B
Muthuswamy
Senthil
S
Muller
William J
WJ
D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000235:genetics*; D049109:Cell Proliferation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007365:Intercellular Junctions / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout
D048948:14-3-3 Proteins; C499130:Sfn protein, mouse