The E2F1 Oncogene Transcriptionally Regulates NELL2 in Cancer Cells
Authors: Yun-Gil Roh
Sun-Hee Leem
Byung Ju Lee
Seung Il Kim
Sang-Yeop Lee
Hyun Hee Lee
Dong Hee Kim
Journal: DNA and Cell Biology (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: NELL2; E2F1; cancer progression; cell proliferation; cell survival
Affiliations: Department of Biological Science, College of Natural Sciences, Dong-A University, Busan, South Korea., Division of Life Science, Korea Basic Science Institute, Daejeon, South Korea., Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea.

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. 

Retracted: Yes

PubPeer comments:
 Figure 5A appears to have at least one repeated image. ***  ***  , 
 Retracted [4 April 2022] . --------------- The publisher of the journal contacted all authors listed on the paper to inquire about the problems identified on PubPeer. The lead author, Dr. Dong Hee Kim, responded by stating, u201cThere seems to be a problem in the processing of working on the figures,u201d and supplied a new figure to replace the duplicated image. After reviewing the newly supplied figure and the author s answer, the Editor of the journal found the author s response to be unacceptable and called for a full retraction of the published paper. *DNA and Cell Biology* is committed to upholding the rigors of scientific publishing and the veracity of the literature. , 
 Dear Editor, Thank you for your e-mail, we identified two problem during checking the Figure 5. It was confirmed that not only the duplication image, but also the order of the Figure 5A of E2F1 and E2F1+NELL2 groups were changed in 5637 cells. According to our results, overexpression of NELL2 or E2F1 showed an increase of invasiveness in both cell lines. Moreover, an enhanced effect from cotransfection with E2F1 and NELL2 was detected in transfected cells So, we have attached a corrected Figure 5A, please check in figure. Please reconsider the retraction and let me know if there is a way to reconsider the retraction. we look forward to hearing from you soon. Thanks.  ,