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Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc

Xu, Dakang, Dwyer, Julie, He, Li, Duan, Wei and Liu, Jun-Ping 2008, Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc, Journal of biological chemistry, vol. 283, no. 35, pp. 23567-23580.

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Title Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc
Author(s) Xu, Dakang
Dwyer, Julie
He, Li
Duan, Wei
Liu, Jun-Ping
Journal name Journal of biological chemistry
Volume number 283
Issue number 35
Start page 23567
End page 23580
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Bethesda, Md
Publication date 2008-08-29
ISSN 0021-9258
1083-351X
Summary Human 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.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2008
Copyright notice ©2008, The American Society for Biochemistry and Molecular Biology, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30017818

Document type: Journal Article
Collection: School of Medicine
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Citation counts: TR Web of Science Citation Count  Cited 33 times in TR Web of Science
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