Zhang Yuxiang, Wang Zhiwei, Ahmed Fakhara, Banerjee Sanjeev, Li Yiwei, Sarkar Fazlul H
Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, Beijing, China.
Int J Cancer. 2006 Nov 1;119(9):2071-7. doi: 10.1002/ijc.22077.
Notch is an ancient cell signaling system that regulates cell fate specification, stem cell maintenance and initiation of differentiation in many tissues. It has been reported that Jagged-1, a Notch ligand, is significantly over expressed in metastatic prostate cancer compared to localized prostate cancer or benign prostatic tissues. Therefore, deregulation of Jagged-1 protein levels may play a role in prostate cancer cell growth and progression. Hence, the aim of our current study was to investigate the mechanistic role of Jagged-1 in prostate cancer cell growth and cell cycle progression. Our results show, for the first time, that down-regulation of Jagged-1 induces cell growth inhibition and S phase cell cycle arrest in prostate cancer cells, with reduced CDK2 kinase activity and increased p27 expression. These results suggest that Jagged-1 could be a potential therapeutic target for the treatment of prostate cancer.
Notch是一种古老的细胞信号系统，可调节许多组织中的细胞命运决定、干细胞维持和分化起始。据报道，与局限性前列腺癌或良性前列腺组织相比，Notch配体Jagged-1在转移性前列腺癌中显著过表达。因此，Jagged-1蛋白水平的失调可能在前列腺癌细胞的生长和进展中起作用。因此，我们当前研究的目的是探讨Jagged-1在前列腺癌细胞生长和细胞周期进展中的机制性作用。我们的结果首次表明，Jagged-1的下调诱导前列腺癌细胞的细胞生长抑制和S期细胞周期停滞，同时CDK2激酶活性降低，p27表达增加。这些结果表明，Jagged-1可能是治疗前列腺癌的潜在治疗靶点。
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