title: The E2F1 oncogene transcriptionally regulates NELL2 in cancer cells.
abstract: NELL2 was first identified as a mammalian homolog of the chicken NEL protein. It was expressed in neurons and has been suggested to play a role in cell survival. However, no clear evidence has yet been available for functions of NELL2. In this study, we found two E2F1 binding sites located in the NELL2 promoter region. We examined the expression of NELL2 and E2F1 in human breast cancer cells (MDA-MB231, MCF7) and bladder cancer cells (5637, UC5). In MDA-MB231 and 5637, the expression levels of NELL2 and E2F1 were higher. To examine the interaction between E2F1 and NELL2, the binding activity was checked by a promoter assay and chromatin immunoprecipitation. From the results, we suggest that NELL2 is a novel target gene of E2F1, which is a key regulator of cell proliferation. We reveal that expression of NELL2 is regulated by E2F1, specifically, mRNA and protein levels of NELL2 are elevated upon activation of exogenous E2F1. Moreover, cells overexpressing NELL2 increased their invasive ability and an enhancement of the effect was observed when NELL2 and E2F1 were coexpressed in MDA-MB231 cells. Therefore, we suggest a novel activity for NELL2 in cancer progression through the regulation of E2F1.
authors.affiliation: Department of Biological Science, College of Natural Sciences, Dong-A University, Busan, South Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Yun-Gil
authors.initials: YG
authors.lastname: Roh
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Sang-Yeop
authors.initials: SY
authors.lastname: Lee
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
mesh_terms: D001665:Binding Sites; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D018450:Disease Progression; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C104145:NELL2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger