Y-box binding protein-1 (YB-1) promotes cell cycle progression through CDC6-dependent pathway in human cancer cells.
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 p21(Cip1) and p16(INK4A) 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.
Basaki
Yuji
Y
Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Taguchi
Ken-Ichi
K
Izumi
Hiroto
H
Murakami
Yuichi
Y
Kubo
Takuya
T
Hosoi
Fumihito
F
Watari
Kosuke
K
Nakano
Kenji
K
Kawaguchi
Hidetoshi
H
Ohno
Shinji
S
Kohno
Kimitoshi
K
Ono
Mayumi
M
Kuwano
Michihiko
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D051840:Y-Box-Binding Protein 1