An EBF3-mediated transcriptional program that induces cell cycle arrest and apoptosis

Lisa Y. Zhao, Yuxin Niu, Aleixo Santiago, Jilin Liu, Sara H. Albert, Keith D. Robertson, Daiqing Liao

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


In a genome-wide screen for putative tumor suppressor genes, the EBF3 locus on the human chromosome 10q26.3 was found to be deleted or methylated in 73% of the examined cases of brain tumors. EBF3 is expressed in normal brain but is silenced in brain tumors. Therefore, it is suggested that EBF3 is a tumor suppressor. However, it remains unknown whether inactivation of EBF3 locus also occurs in other types of tumors and what functions of EBF3 underlie EBF3-mediated tumor suppression. We show here that expression of EBF3 resulted in cell cycle arrest and apoptosis. The expression of cyclin-dependent kinase inhibitors was profoundly affected with early activation and then repression of p21cip1/waf1 and persistent activation of both p27kip1 and p57kip2, whereas genes involved in cell survival and proliferation were suppressed. EBF3 bound directly to p21cip1/waf1 promoter and regulated transcription from both p21cip1/waf1 and p27kip1 promoters in reporter assays. Apoptosis occurred 48 hours after EBF3 expression with caspase-3 activation. Silencing of the EBF3 locus was observed in brain, colorectal, breast, liver, and bone tumor cell lines and its reactivation was achieved on treatment with 5-aza-2′-deoxycytidine and trichostatin A in a significant portion of these tumor cells. Therefore, EBF3 regulates a transcriptional program underlying a putative tumor suppression pathway.

Original languageEnglish (US)
Pages (from-to)9445-9452
Number of pages8
JournalCancer research
Issue number19
StatePublished - Oct 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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