Genomewide transcription profiles altered by BMI1

Authors: JiHye Lee Changhee Min SahngJune Kwak YeonSun Seong

Publish Date: 2012/12/20

Volume: 6, Issue: 4, Pages: 362-371

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Abstract

Cyclindependent kinases CDKs are highly conserved over evolutionary path and function as master regulators of the cell division cycle Thus CDK inhibitors have been focused in the drug development for cancer and other cell proliferative disorders Among these inhibitors Roscovitine is well known compound and under clinical trial currently while far less has been reported on another CDK inhibitor — BMI1026 designed as a drug candidate also targeting the cell cycle In this study we tried to define biological effects and possible mechanisms of the two chemicals by analyzing the altered transcriptome profiles when BMI1026 and Roscovitine are applied on WI38 cells Our result revealed both BMI1026 and Roscovitine produced similar gene expression profiles where E2F target genes were suppressed in common including cyclin A MCM3 and PCNA along with activated p53 pathway This finding strongly indicates that molecular machineries responsible for other established senescence models are also employed in the changes in WI38 cells induced by the two CDK inhibitors

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