A functional role of Par-4 in endometrial tumorigenesis

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Constitutively high levels of Par-4 expression were observed in epithelial cells through the menstrual cycle, in contrast to the transient up-regulation in stromal components in the menstrual stage, positively correlated with the phospho-p65 and apoptosis. Most ECs exhibited significant down-regulation, with positive links only to pp65 expression. Transfection of p65 led to transactivation of Par-4. Overexpression of Par-4 resulted in induction of not only apoptosis but also senescence, through changes in expression of bcl-2 and p21WAF1, respectively. Together, these findings suggest that a signaling cascade involving sequential activation of NF-_κB/p65 and Par-4 may participate in relatively early events of endometrial tumorigenesis, leading to modulation of cell kinetics including apoptosis and cell cycle progression.