RRC ID 45046
Author Harada M, Kotake Y, Ohhata T, Kitagawa K, Niida H, Matsuura S, Funai K, Sugimura H, Suda T, Kitagawa M.
Title YB-1 promotes transcription of cyclin D1 in human non-small-cell lung cancers.
Journal Genes Cells
Abstract Cyclin D1, an oncogenic G1 cyclin, and YB-1, a transcription factor involved in cell growth, are both over-expressed in several human cancers. In human lung cancer, the functional association between YB-1 and cyclin D1 has never been elucidated. In this study, we show YB-1 is involved in the transcription of cyclin D1 in human lung cancer. Depletion of endogenous YB-1 by siRNA inhibited progression of G1 phase and down-regulated both the protein and mRNA levels of cyclin D1 in human lung cancer cells. Forced over-expression of YB-1 with a cyclin D1 reporter plasmid increased luciferase activity, and ChIP assay results showed YB-1 bound to the cyclin D1 promoter. Moreover, the amount of YB-1 mRNA positively correlated with cyclin D1 mRNA levels in clinical non-small-cell lung cancer (NSCLC) specimens. Immunohistochemical analysis also indicated YB-1 expression correlated with cyclin D1 expression in NSCLC specimens. In addition, most of the cases expressing both cyclin D1 and CDC6, another molecule controlled by YB-1, had co-existing YB-1 over-expression. Together, our results suggest that aberrant expression of both cyclin D1 and CDC6 by YB-1 over-expression may collaboratively participate in lung carcinogenesis.
Volume 19(6)
Pages 504-16
Published 2014-6-1
DOI 10.1111/gtc.12150
PMID 24774443
MeSH Adenocarcinoma / metabolism Adenocarcinoma / pathology Adult Aged Aged, 80 and over Carcinoma, Large Cell / metabolism Carcinoma, Large Cell / pathology Carcinoma, Non-Small-Cell Lung / metabolism* Carcinoma, Non-Small-Cell Lung / pathology Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Proliferation Cyclin D1 / genetics* Cyclin D1 / metabolism Female Gene Knockdown Techniques Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology Male Middle Aged Nuclear Proteins / genetics Nuclear Proteins / metabolism Promoter Regions, Genetic RNA, Messenger / metabolism Y-Box-Binding Protein 1 / genetics Y-Box-Binding Protein 1 / metabolism*
IF 1.922
Times Cited 27
Human and Animal Cells