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Downregulation of nucleostemin causes G1 cell cycle arrest via a p53-independent pathway in prostate cancer PC-3 cells.

作者信息

Liu Ranlu, Zhang Zhihong, Xu Yong

机构信息

Tianjin Institute of Urology and Department of Urology, Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Urol Int. 2010;85(2):221-7. doi: 10.1159/000315968. Epub 2010 Jul 21.

DOI:10.1159/000315968
PMID:20664182
Abstract

AIMS

To screen the genes and possible signal transduction pathways with which nucleostemin (NS) interacts and explore the mechanism of NS in prostate cancer.

METHODS

NS-specific short-hairpin RNA expression plasmid was used to downregulate the NS level in PC-3 cells and the changes of cell cycle were studied. After that, oligonucleotide DNA microarray was used to screen the genome changes in PC-3 cells and quantitative real-time PCR was used to further confirm the differentially expressed genes.

RESULTS

Detection of cell cycle showed a decrease of S stage and an increase of G1 stage after downregulation of NS. 219 differentially expressed genes were found and these genes were involved in cell cycle, cell proliferation, signal transduction, cell apoptosis and cell differentiation, and so on. Genes related to cell cycle were discussed emphatically. INK4 family genes (P15, P16, P18) were upregulated while cyclin D1 HDAC1 were downregulated. These genes were tightly related to CDK4/6-cyclin D and pRb-E2F1 complexes.

CONCLUSION

NS is an important G1/S checkpoint regulator and it could regulate cell cycles via a p53-independent pathway in prostate cancer.

摘要

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