YB‐1 promotes transcription of cyclin D1 in human non‐small‐cell lung cancers. (29th April 2014) - Harada, Masanori
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.