ESX

A structurally unique Ets overexpressed early during human breast tumorigenesis

Chuan Hsiung Chang, Gary K. Scott, Wen Lin Kuo, Xiaohui Xiong, Yevgeniya Suzdaltseva, John W. Park, Peter Sayre, Katrina Erny, Colin Collins, Joe Gray, Christopher C. Benz

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The > 30 known members of the Ets multigene family of transcriptional regulators are increasingly being recognized for their involvement in early embryonic development and late tissue maturation, directing stage-specific and tissue-restricted programs of target gene expression. Identifiable primarily by their 85 amino acid ETS DNA-binding domain and dispersed across all metazoan lineages into distinct subfamilies, Ets genes also produce malignancies in humans and other vertebrates when overexpressed or rearranged into chimeras retaining the ETS domain, suggesting that their oncogenic potential is determined by the program of target genes they regulate. Searching for Ets factors that regulate expression of the HER2/neu (c-erbB2) oncogene in human breast cancer, we identified a new epithelium-restricted Ets encoding an ETS domain homologous to the Drosophila E74/human Elf-1 subfamily, an amino-terminal region (A-region or Pointed domain) homologous to the distantly related Ets-1 subfamily, and a serine-rich box homologous to the transactivating domain of the lymphocyte-restricted High Mobility Group (HMG) protein, SOX4. Recombinant protein encoded by ESX (for epithelial-restricted with serine box) exhibits Ets-like DNA binding specificity in electrophoretic mobility shift assays and, in transient transfection assays, transactivates Ets-responsive promoter elements including that found in the HER2/neu oncogene, ESX is located at chromosome 1q32 in a region known to be amplified in 50% of early breast cancers, is heregulin-inducible and overexpressed in HER2/neu activated breast cancer cells. Tissue hybridization suggests that ESX becomes overexpressed at an early stage of human breast cancer development known as ductal carcinoma in situ (DCIS).

Original languageEnglish (US)
Pages (from-to)1617-1622
Number of pages6
JournalOncogene
Volume14
Issue number13
StatePublished - 1997
Externally publishedYes

Fingerprint

Carcinogenesis
Breast
Breast Neoplasms
Oncogenes
Serine
Neuregulin-1
High Mobility Group Proteins
Carcinoma, Intraductal, Noninfiltrating
DNA
Electrophoretic Mobility Shift Assay
Multigene Family
Recombinant Proteins
Genes
Drosophila
Embryonic Development
Transfection
Vertebrates
Epithelium
Chromosomes
Lymphocytes

Keywords

  • Breast cancer
  • Epithelial-restricted
  • Ets
  • HER2/neu

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Chang, C. H., Scott, G. K., Kuo, W. L., Xiong, X., Suzdaltseva, Y., Park, J. W., ... Benz, C. C. (1997). ESX: A structurally unique Ets overexpressed early during human breast tumorigenesis. Oncogene, 14(13), 1617-1622.

ESX : A structurally unique Ets overexpressed early during human breast tumorigenesis. / Chang, Chuan Hsiung; Scott, Gary K.; Kuo, Wen Lin; Xiong, Xiaohui; Suzdaltseva, Yevgeniya; Park, John W.; Sayre, Peter; Erny, Katrina; Collins, Colin; Gray, Joe; Benz, Christopher C.

In: Oncogene, Vol. 14, No. 13, 1997, p. 1617-1622.

Research output: Contribution to journalArticle

Chang, CH, Scott, GK, Kuo, WL, Xiong, X, Suzdaltseva, Y, Park, JW, Sayre, P, Erny, K, Collins, C, Gray, J & Benz, CC 1997, 'ESX: A structurally unique Ets overexpressed early during human breast tumorigenesis', Oncogene, vol. 14, no. 13, pp. 1617-1622.
Chang CH, Scott GK, Kuo WL, Xiong X, Suzdaltseva Y, Park JW et al. ESX: A structurally unique Ets overexpressed early during human breast tumorigenesis. Oncogene. 1997;14(13):1617-1622.
Chang, Chuan Hsiung ; Scott, Gary K. ; Kuo, Wen Lin ; Xiong, Xiaohui ; Suzdaltseva, Yevgeniya ; Park, John W. ; Sayre, Peter ; Erny, Katrina ; Collins, Colin ; Gray, Joe ; Benz, Christopher C. / ESX : A structurally unique Ets overexpressed early during human breast tumorigenesis. In: Oncogene. 1997 ; Vol. 14, No. 13. pp. 1617-1622.
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