duan-ets2maintainshtert-2008.pdf (876.85 kB)
Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc
journal contribution
posted on 2008-08-29, 00:00 authored by D Xu, J Dwyer, L He, Wei DuanWei Duan, J P LiuHuman telomerase reverse transcriptase (hTERT) underlies cancer cell immortalization, and the expression of hTERT is regulated strictly at the gene transcription. Here, we report that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation. Silencing Ets2 induces a decrease of hTERT gene expression and increase in human breast cancer cell death. Reconstitution with recombinant hTERT rescues the apoptosis induced by Ets2 depression. In vitro and in vivo analyses show that Ets2 binds to the EtsA and EtsB DNA motifs on the hTERT gene promoter. Mutation of either Ets2 binding site reduces the hTERT promoter transcriptional activity. Moreover, Ets2 forms a complex with c-Myc as demonstrated by co-immunoprecipitation and glutathione S-transferase pulldown assays. Immunological depletion of Ets2, or mutation of the EtsA DNA motif, disables c-Myc binding to the E-box, whereas removal of c-Myc or mutation of the E-box also compromises Ets2 binding to EtsA. Thus, hTERT gene expression is maintained by a mechanism involving Ets2 interactions with the c-Myc transcription factor and the hTERT gene promoter, a protein-DNA complex critical for hTERT gene expression and breast cancer cell proliferation.
History
Journal
Journal of biological chemistryVolume
283Issue
35Pagination
23567 - 23580Publisher
American Society for Biochemistry and Molecular BiologyLocation
Bethesda, MdPublisher DOI
Link to full text
ISSN
0021-9258eISSN
1083-351XLanguage
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2008, The American Society for Biochemistry and Molecular Biology, Inc.Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC