TY - JOUR
T1 - ESX
T2 - A structurally unique Ets overexpressed early during human breast tumorigenesis
AU - Chang, Chuan Hsiung
AU - Scott, Gary K.
AU - Kuo, Wen Lin
AU - Xiong, Xiaohui
AU - Suzdaltseva, Yevgeniya
AU - Park, John W.
AU - Sayre, Peter
AU - Erny, Katrina
AU - Collins, Colin
AU - Gray, Joe W.
AU - Benz, Christopher C.
N1 - Funding Information:
We thank Helene Smith for the normal mammary epithelial cells, Britt-Marie Ljung, Karen Chew, Ann Thor, and Susan Edgerton for tissue samples and histologic assistance. This work was supported in part by NIH sponsored multi-institutional program project (CA44768) and SPORE grants (CA58207), an NIH sponsored individual research grant (CA36773), as well as the Hazel P Munroe and Janet Landfear memorial funds. K Erny is a fellowship recipient from the Swiss Cancer League. ESX cDNA sequence including the full-length reading frame have been deposited in GenBank (accession number U66894).
PY - 1997
Y1 - 1997
N2 - 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).
AB - 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).
KW - Breast cancer
KW - Epithelial-restricted
KW - Ets
KW - HER2/neu
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U2 - 10.1038/sj.onc.1200978
DO - 10.1038/sj.onc.1200978
M3 - Article
C2 - 9129154
AN - SCOPUS:8244259923
SN - 0950-9232
VL - 14
SP - 1617
EP - 1622
JO - Oncogene
JF - Oncogene
IS - 13
ER -