Inhibitory mechanism of cell proliferation by a novel X-linked tumor suppressor Nrk

点击翻译按钮获取中文摘要

1) We identified CSIG (cellular senescence-inhibited gene), a protein which inhibits PTEN in the Akt signal transduction pathway, as a Nrk-binding protein in placenta, suggesting that Nrk inhibits the proliferation of spongiotrophoblasts in placenta by inhibiting the Akt signaling pathway. We also found that the level of a cell cycle inhibitor protein p27 is downregulated in Nrk knockout spongiotrophoblasts, suggesting that Nrk increases p27 gene expression or inhibits p27 protein degradation in spongiotrophoblasts.2) We found that the estrogen level is elevated in the blood and ovary of mammary tumor-harboring Nrk knockout female mice, suggesting that the high estrogen level in the blood causes mammary tumors in Nrk knockout mice. In addition, we found that Nrk is expressed in lactating and old (~12 months) wild-type mice, suggesting that Nrk suppresses the overgrowth of mammary epithelial cells by downregulating estrogen synthesis in the ovary.