Down-regulation of Jagged-1 induces cell growth inhibition and S phase arrest in prostate cancer cells.
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.
Zhang
Yuxiang
Y
Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, Beijing, China.
Wang
Zhiwei
Z
Ahmed
Fakhara
F
Banerjee
Sanjeev
S
Li
Yiwei
Y
Sarkar
Fazlul H
FH
D002135:Calcium-Binding Proteins / Q000235:genetics*; D002455:Cell Division; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D000072099:Serrate-Jagged Proteins; D051357:Cyclin-Dependent Kinase 2