Details

Autor(en) / Beteiligte

• ZHAO, Lisa Y
• YUXIN NIU
• SANTIAGO, Aleixo
• JILIN LIU
• ALBERT, Sara H
• ROBERTSON, Keith D
• DAIQING LIAO

Titel

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

Ist Teil von

• Cancer research (Chicago, Ill.), 2006-10, Vol.66 (19), p.9445-9452

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 p21(cip1/waf1) and persistent activation of both p27(kip1) and p57(kip2), whereas genes involved in cell survival and proliferation were suppressed. EBF3 bound directly to p21(cip1/waf1) promoter and regulated transcription from both p21(cip1/waf1) and p27(kip1) 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.