Icilin inhibits E2F1-mediated cell cycle regulatory programs in prostate cancer.
Aberrant expression of cell cycle regulators have been implicated in prostate cancer development and progression. Therefore, understanding transcriptional networks controlling the cell cycle remain a challenge in the development of prostate cancer treatment. In this study, we found that icilin, a super-cooling agent, down-regulated the expression of cell cycle signature genes and caused G1 arrest in PC-3 prostate cancer cells. With reverse-engineering and an unbiased interrogation of a prostate cancer-specific regulatory network, master regulator analysis discovered that icilin affected cell cycle-related transcriptional modules and identified E2F1 transcription factor as a target master regulator of icilin. Experimental analyses confirmed that icilin reduced the activity and expression levels of E2F1. These results demonstrated that icilin inactivates a small regulatory module controlling the cell cycle in prostate cancer cells. Our study might provide insight into the development of cell cycle-targeted cancer therapeutics.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
Sanghoon
S
Lee
Jung Nyeo
JN
Chun
Su-Hwa
SH
Kim
Insuk
I
So
Ju-Hong
JH
Jeon
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004278:DNA, Superhelical / Q000187:drug effects*; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011744:Pyrimidinones / Q000494:pharmacology*
D004278:DNA, Superhelical; D050687:E2F1 Transcription Factor; D011744:Pyrimidinones; C490483:icilin
Bioinformatics; Gene expression profiling; Icilin; Microarray; Prostate cancer