TY - JOUR
T1 - Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells
AU - Basaki, Yuji
AU - Taguchi, Ken ichi
AU - Izumi, Hiroto
AU - Murakami, Yuichi
AU - Kubo, Takuya
AU - Hosoi, Fumihito
AU - Watari, Kosuke
AU - Nakano, Kenji
AU - Kawaguchi, Hidetoshi
AU - Ohno, Shinji
AU - Kohno, Kimitoshi
AU - Ono, Mayumi
AU - Kuwano, Michihiko
N1 - Funding Information:
This research was supported by a grant-in-aid for Scientific Research on Priority Areas, Cancer, from the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.O.), and by the 3rd Term Comprehensive Control Research for Cancer from the Ministry of Health, Labor and Welfare, Japan (M.K.). This study was also supported, in part, by the Formation of Innovation Center for Fusion of Advanced Technologies, Kyushu University, Japan (M.K. and M.O.). We thank R.G. Deeley (Cancer Research Institute at Queen’s University) for fruitful discussions.
PY - 2010/3
Y1 - 2010/3
N2 - Y-box binding protein-1 (YB-1) plays pivotal roles in acquisition of global drug resistance and cell growth promotion through transcriptional activation of genes for both drug resistance and growth factor receptors. In this study, we investigated whether YB-1 is involved in regulation of the cell cycle and cell proliferation of human cancer cells. Treatment with YB-1 siRNA caused a marked suppression of cell proliferation and expression of a cell cycle related gene, CDC6 by cancer cells. Of cell cycle of cancer cells, S phase content was specifically reduced by knockdown of YB-1. The overexpression of CDC6 abrogated this inhibition of both cell proliferation and S phase entry. ChIP assay demonstrated that YB-1 binds to a Y-box located in the promoter region of the CDC6 gene. Expression of cyclin D1, CDK1 and CDK2 was also reduced with increased expression of p21Cip1 and p16INK4A when treated with YB-1 siRNA. Furthermore, the nuclear YB-1 expression was significantly associated with the level of CDC6 nuclear expression in patients with breast cancer. In conclusion, YB-1 plays an important role in cell cycle progression at G1/S of human cancer cells. YB-1 thus could be a potent biomarker for tumour growth and cell cycle in its close association with CDC6.
AB - Y-box binding protein-1 (YB-1) plays pivotal roles in acquisition of global drug resistance and cell growth promotion through transcriptional activation of genes for both drug resistance and growth factor receptors. In this study, we investigated whether YB-1 is involved in regulation of the cell cycle and cell proliferation of human cancer cells. Treatment with YB-1 siRNA caused a marked suppression of cell proliferation and expression of a cell cycle related gene, CDC6 by cancer cells. Of cell cycle of cancer cells, S phase content was specifically reduced by knockdown of YB-1. The overexpression of CDC6 abrogated this inhibition of both cell proliferation and S phase entry. ChIP assay demonstrated that YB-1 binds to a Y-box located in the promoter region of the CDC6 gene. Expression of cyclin D1, CDK1 and CDK2 was also reduced with increased expression of p21Cip1 and p16INK4A when treated with YB-1 siRNA. Furthermore, the nuclear YB-1 expression was significantly associated with the level of CDC6 nuclear expression in patients with breast cancer. In conclusion, YB-1 plays an important role in cell cycle progression at G1/S of human cancer cells. YB-1 thus could be a potent biomarker for tumour growth and cell cycle in its close association with CDC6.
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U2 - 10.1016/j.ejca.2009.12.024
DO - 10.1016/j.ejca.2009.12.024
M3 - Article
C2 - 20079629
AN - SCOPUS:77349094312
VL - 46
SP - 954
EP - 965
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
SN - 0959-8049
IS - 5
ER -
