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Gene Review

ELF3  -  E74-like factor 3 (ets domain...

Homo sapiens

Synonyms: E74-like factor 3, EPR-1, ERT, ESE-1, ESX, ...
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Disease relevance of ELF3


Psychiatry related information on ELF3


High impact information on ELF3

  • When ERT is contraindicated, viable alternatives to retard bone loss and/or control vasomotor symptoms include calcium supplementation and progestin therapy [10].
  • METHODS: In a 5-year multicenter, double-blind, randomized, placebo-controlled osteoporosis prevention trial, healthy postmenopausal women who had undergone hysterectomy less than 15 years before the study and had no history of breast cancer received placebo, raloxifene (at one of two doses), or conjugated estrogens (ERT) [11].
  • Within treatment groups, the mean breast density from baseline to 2 years decreased statistically significantly in women receiving the placebo or either the higher or lower raloxifene dose (P = 0.003, P = 0.002, and P<0.001, respectively) and showed a nonstatistically significant increase in women receiving ERT [11].
  • ERT for survivors of endometrial cancer? A new trial will resolve debate [12].
  • INTERPRETATION: Current ERT reduced primarily sudden cardiac death and predicted reduced cardiovascular mortality, but did not reduce morbidity [13].

Chemical compound and disease context of ELF3


Biological context of ELF3


Anatomical context of ELF3

  • In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its effect on the human keratin 4 gene promoter based upon the role of keratin 4 in early differentiation of the esophageal squamous epithelium [21].
  • Expression of the ETS transcription factor ELF3 in the retinal pigment epithelium [18].
  • Moreover, the induction of ESE-1 in response to inflammatory cytokine interleukin-1 is associated with a parallel increase of the expression of p300 in vascular endothelial cells, suggesting that in the setting of inflammation, the transcriptional activity of ESE-1 is positively modulated by interaction with the transcriptional co-activator p300 [22].
  • Finally, Ang-1 and ESE-1 exhibit a similar and strong expression pattern in the synovium of patients with rheumatoid arthritis [19].
  • ESX induces transformation and functional epithelial to mesenchymal transition in MCF-12A mammary epithelial cells [20].

Associations of ELF3 with chemical compounds

  • Infection of this cell line with a retroviral construct expressing ERT induced higher levels of endogenous RII mRNA expression and protein expression relative to cells infected with chloramphenicol acetyltransferase (CATneo) as a control [23].
  • ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain [24].
  • ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage [25].
  • BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass [26].
  • A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1) [27].

Physical interactions of ELF3

  • The newly identified epithelium-specific ets transcription factor ERT/ESX/ESE-1 binds to the TGF-beta RII promoter and induces promoter activity [28].
  • Transient transfection experiments confirmed the ability of this TBP-binding transactivation domain in ESX to squelch heterologous promoters independent of any promoter binding as efficiently as the transactivation domain from VP16 [29].

Regulatory relationships of ELF3

  • Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter [21].
  • CONCLUSIONS: The ELF3 transcription factor is highly expressed in the RPE and can regulate important ocular genes, such as TIMP3, in vitro [18].
  • In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells [23].
  • Interestingly, Ku70 and Ku 86 negatively regulate the transcriptional activity of ESE-1 [22].
  • Elf3 upregulated the TIMP3 promoter, with Elf3a and -3b inducing an approximate sixfold increase in activity [18].
  • These findings provide novel insights into the mechanism of transformation potential of ESE-1 and discovered that ESE-1 functions are coordinately regulated by Pak1 phosphorylation and beta-TrCP-dependent ubiquitin-proteasome pathways [30].

Other interactions of ELF3


Analytical, diagnostic and therapeutic context of ELF3

  • The Ku proteins inhibit the ability of ESE-1 to bind to oligonucleotide probes in gel mobility shift assays [22].
  • Luciferase reporter assays demonstrated that the presence of the Ets-binding site at -150 in the promoter region of the claudin7 gene was critical for the transcriptional activity, and gel shift and chromatin immunoprecipitation assays confirmed the binding of ELF3 to the Ets site at -150 [31].
  • ELF3 was confirmed to be more highly expressed in biphasic than monophasic SS by real-time quantitative PCR [32].
  • We also examined ELF3, a transcription factor associated with epithelial differentiation in SS in a previous cDNA microarray, by RT-PCR [32].
  • This exon 4-encoded 31 amino acid domain in ESX was shown by mutation and deletion analysis to possess a 13 residue acidic transactivation core which, based on modeling and circular dichroism analysis, is predicted to form an amphipathic alpha-helical secondary structure [29].


  1. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Allander, S.V., Illei, P.B., Chen, Y., Antonescu, C.R., Bittner, M., Ladanyi, M., Meltzer, P.S. Am. J. Pathol. (2002) [Pubmed]
  2. A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer. Tymms, M.J., Ng, A.Y., Thomas, R.S., Schutte, B.C., Zhou, J., Eyre, H.J., Sutherland, G.R., Seth, A., Rosenberg, M., Papas, T., Debouck, C., Kola, I. Oncogene (1997) [Pubmed]
  3. Partially unspliced and fully spliced ELF3 mRNA, including a new Alu element in human breast cancer. Kaplan, M.H., Wang, X.P., Xu, H.P., Dosik, M.H. Breast Cancer Res. Treat. (2004) [Pubmed]
  4. Sequence-specific enhancer binding protein is responsible for the differential expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines: Implication for the loss of TGF-beta type II receptor expression. Park, S.H., Kim, Y.S., Park, B.K., Hougaard, S., Kim, S.J. Oncogene (2001) [Pubmed]
  5. The oxidative metabolism of estrogen modulates response to ERT/HRT in postmenopausal women. Armamento-Villareal, R.C., Napoli, N., Klug, T., Civitelli, R. Bone (2004) [Pubmed]
  6. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer and a review of possible alternatives. Pritchard, K.I. Ann. Oncol. (2001) [Pubmed]
  7. Is there a role for estrogen replacement therapy in the prevention and treatment of dementia? Birge, S.J. Journal of the American Geriatrics Society. (1996) [Pubmed]
  8. Tobacco smoking and oestrogen replacement are associated with lower total and central fat in monozygotic twins. Samaras, K., Kelly, P.J., Spector, T.D., Chiano, M.N., Campbell, L.V. Int. J. Obes. Relat. Metab. Disord. (1998) [Pubmed]
  9. Alcohol, estrogen replacement therapy, and visuospatial processes in postmenopausal women. Tivis, L.J., Green, M.D., Nixon, S.J., Tivis, R.D. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  10. Hormone replacement therapy in the menopause: a pro opinion. Smith, H.O., Kammerer-Doak, D.N., Barbo, D.M., Sarto, G.E. CA: a cancer journal for clinicians. (1996) [Pubmed]
  11. Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo. Freedman, M., San Martin, J., O'Gorman, J., Eckert, S., Lippman, M.E., Lo, S.C., Walls, E.L., Zeng, J. J. Natl. Cancer Inst. (2001) [Pubmed]
  12. ERT for survivors of endometrial cancer? A new trial will resolve debate. McNeil, C. J. Natl. Cancer Inst. (1997) [Pubmed]
  13. Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT). Sourander, L., Rajala, T., Räihä, I., Mäkinen, J., Erkkola, R., Helenius, H. Lancet (1998) [Pubmed]
  14. Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study. van Baal, W.M., Emeis, J.J., van der Mooren, M.J., Kessel, H., Kenemans, P., Stehouwer, C.D. Thromb. Haemost. (2000) [Pubmed]
  15. The case for less-than-monthly progestogen in women on HT: is transvaginal ultrasound the key? Goldstein, S.R. Menopause (New York, N.Y.) (2005) [Pubmed]
  16. Metabolic effects of tamoxifen in postmenopause. Sismondi, P., Biglia, N., Giai, M., Sgro, L., Campagnoli, C. Anticancer Res. (1994) [Pubmed]
  17. Safety of estrogen/androgen regimens. Simon, J.A. The Journal of reproductive medicine. (2001) [Pubmed]
  18. Expression of the ETS transcription factor ELF3 in the retinal pigment epithelium. Jobling, A.I., Fang, Z., Koleski, D., Tymms, M.J. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  19. ESE-1 is a novel transcriptional mediator of angiopoietin-1 expression in the setting of inflammation. Brown, C., Gaspar, J., Pettit, A., Lee, R., Gu, X., Wang, H., Manning, C., Voland, C., Goldring, S.R., Goldring, M.B., Libermann, T.A., Gravallese, E.M., Oettgen, P. J. Biol. Chem. (2004) [Pubmed]
  20. ESX induces transformation and functional epithelial to mesenchymal transition in MCF-12A mammary epithelial cells. Schedin, P.J., Eckel-Mahan, K.L., McDaniel, S.M., Prescott, J.D., Brodsky, K.S., Tentler, J.J., Gutierrez-Hartmann, A. Oncogene (2004) [Pubmed]
  21. Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation. Brembeck, F.H., Opitz, O.G., Libermann, T.A., Rustgi, A.K. Oncogene (2000) [Pubmed]
  22. Positive and negative modulation of the transcriptional activity of the ETS factor ESE-1 through interaction with p300, CREB-binding protein, and Ku 70/86. Wang, H., Fang, R., Cho, J.Y., Libermann, T.A., Oettgen, P. J. Biol. Chem. (2004) [Pubmed]
  23. Over-expression of ERT(ESX/ESE-1/ELF3), an ets-related transcription factor, induces endogenous TGF-beta type II receptor expression and restores the TGF-beta signaling pathway in Hs578t human breast cancer cells. Chang, J., Lee, C., Hahm, K.B., Yi, Y., Choi, S.G., Kim, S.J. Oncogene (2000) [Pubmed]
  24. The ETS transcription factor ESE-1 transforms MCF-12A human mammary epithelial cells via a novel cytoplasmic mechanism. Prescott, J.D., Koto, K.S., Singh, M., Gutierrez-Hartmann, A. Mol. Cell. Biol. (2004) [Pubmed]
  25. ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene. Rudders, S., Gaspar, J., Madore, R., Voland, C., Grall, F., Patel, A., Pellacani, A., Perrella, M.A., Libermann, T.A., Oettgen, P. J. Biol. Chem. (2001) [Pubmed]
  26. Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized, double-blind, placebo-controlled trial. Civitelli, R., Pilgram, T.K., Dotson, M., Muckerman, J., Lewandowski, N., Armamento-Villareal, R., Yokoyama-Crothers, N., Kardaris, E.E., Hauser, J., Cohen, S., Hildebolt, C.F. Arch. Intern. Med. (2002) [Pubmed]
  27. Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss. Lukert, B.P., Johnson, B.E., Robinson, R.G. J. Bone Miner. Res. (1992) [Pubmed]
  28. Effect of ets-related transcription factor (ERT) on transforming growth factor (TGF)-beta type II receptor gene expression in human cancer cell lines. Lee, H.J., Chang, J.H., Kim, Y.S., Kim, S.J., Yang, H.K. J. Exp. Clin. Cancer Res. (2003) [Pubmed]
  29. Exon 4-encoded acidic domain in the epithelium-restricted Ets factor, ESX, confers potent transactivating capacity and binds to TATA-binding protein (TBP). Chang, C.H., Scott, G.K., Baldwin, M.A., Benz, C.C. Oncogene (1999) [Pubmed]
  30. Phosphorylation-dependent regulation of stability and transforming potential of ETS transcriptional factor ESE-1 by p21-activated kinase 1. Manavathi, B., Rayala, S.K., Kumar, R. J. Biol. Chem. (2007) [Pubmed]
  31. Expression of Claudin7 Is Tightly Associated with Epithelial Structures in Synovial Sarcomas and Regulated by an Ets Family Transcription Factor, ELF3. Kohno, Y., Okamoto, T., Ishibe, T., Nagayama, S., Shima, Y., Nishijo, K., Shibata, K.R., Fukiage, K., Otsuka, S., Uejima, D., Araki, N., Naka, N., Nakashima, Y., Aoyama, T., Nakayama, T., Nakamura, T., Toguchida, J. J. Biol. Chem. (2006) [Pubmed]
  32. E-cadherin mutation and Snail overexpression as alternative mechanisms of E-cadherin inactivation in synovial sarcoma. Saito, T., Oda, Y., Kawaguchi, K., Sugimachi, K., Yamamoto, H., Tateishi, N., Tanaka, K., Matsuda, S., Iwamoto, Y., Ladanyi, M., Tsuneyoshi, M. Oncogene (2004) [Pubmed]
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