Oestrogen receptor-α (ERα) is a ligand-dependent transcription factor that primarily mediates oestrogen (E2)-dependent gene transcription required for mammary gland development. Coregulators critically regulate ERα transcription functions by directly interacting with it. In the present study, we report that ELF3, an epithelial-specific ETS transcription factor, acts as a transcriptional repressor of ERα. Co-immunoprecipitation (Co-IP) analysis demonstrated that ELF3 strongly binds to ERα in the absence of E2, but ELF3 dissociation occurs upon E2 treatment in a dose- and time-dependent manner suggesting that E2 negatively influences such interaction. Domain mapping studies further revealed that the ETS (E-twenty six) domain of ELF3 interacts with the DNA binding domain of ERα. Accordingly, ELF3 inhibited ERα’s DNA binding activity by preventing receptor dimerization, partly explaining the mechanism by which ELF3 represses ERα transcriptional activity. Ectopic expression of ELF3 decreases ERα transcriptional activity as demonstrated by oestrogen response elements (ERE)-luciferase reporter assay or by endogenous ERα target genes. Conversely ELF3 knockdown increases ERα transcriptional activity. Consistent with these results, ELF3 ectopic expression decreases E2-dependent MCF7 cell proliferation whereas ELF3 knockdown increases it. We also found that E2 induces ELF3 expression in MCF7 cells suggesting a negative feedback regulation of ERα signalling in breast cancer cells. A small peptide sequence of ELF3 derived through functional interaction between ERα and ELF3 could inhibit DNA binding activity of ERα and breast cancer cell growth. These findings demonstrate that ELF3 is a novel transcriptional repressor of ERα in breast cancer cells. Peptide interaction studies further represent a novel therapeutic option in breast cancer therapy.
Skip Nav Destination
Close
Article navigation
April 2016
-
Cover Image
Cover Image
Collagen helical symmetry varies with its amino acid sequence: shown is a helix with seventeen-fold symmetry, this is a good representation for the average conformation of the entire collagen molecule. For further details see pp. 1001-1025. Image kindly provided by Dr Jordi Bella.Close Modal - PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 08 2016
A transcriptional repressive role for epithelial-specific ETS factor ELF3 on oestrogen receptor alpha in breast cancer cells
Vijaya Narasihma Reddy Gajulapalli
;
Vijaya Narasihma Reddy Gajulapalli
*Molecular and Cellular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
Search for other works by this author on:
Venkata Subramanyam Kumar Samanthapudi
;
Venkata Subramanyam Kumar Samanthapudi
*Molecular and Cellular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
Search for other works by this author on:
Madhusudana Pulaganti
;
Madhusudana Pulaganti
†Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515003, Andhra Pradesh, India
Search for other works by this author on:
Saratchandra Singh Khumukcham
;
Saratchandra Singh Khumukcham
*Molecular and Cellular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
Search for other works by this author on:
Vijaya Lakhsmi Malisetty
;
Vijaya Lakhsmi Malisetty
‡Department of Biotechnology, Acharya Nagarjuna University, Guntur, Andhra Pradesh, India
Search for other works by this author on:
Lalitha Guruprasad
;
Lalitha Guruprasad
§School of Chemistry, University of Hyderabad, Hyderabad 500046, Telangana, India
Search for other works by this author on:
Suresh Kumar Chitta
;
Suresh Kumar Chitta
†Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515003, Andhra Pradesh, India
Search for other works by this author on:
Bramanandam Manavathi
Bramanandam Manavathi
1
*Molecular and Cellular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, Telangana, India
1To whom correspondence should be addressed (email manavathibsl@uohyd.ernet.in).
Search for other works by this author on:
Biochem J (2016) 473 (8): 1047–1061.
Article history
Received:
June 04 2015
Revision Received:
February 05 2016
Accepted:
February 15 2016
Accepted Manuscript online:
March 02 2016
Citation
Vijaya Narasihma Reddy Gajulapalli, Venkata Subramanyam Kumar Samanthapudi, Madhusudana Pulaganti, Saratchandra Singh Khumukcham, Vijaya Lakhsmi Malisetty, Lalitha Guruprasad, Suresh Kumar Chitta, Bramanandam Manavathi; A transcriptional repressive role for epithelial-specific ETS factor ELF3 on oestrogen receptor alpha in breast cancer cells. Biochem J 15 April 2016; 473 (8): 1047–1061. doi: https://doi.org/10.1042/BCJ20160019
Download citation file:
Close
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Related Articles
Co-repressor complexes and remodelling chromatin for repression
Biochem Soc Trans (August,2000)