ErbB2 activation of ESX gene expression.
Various members of the Ets multigene family exhibit diverse roles in development, cell differentiation, tissue-specific gene expression and human malignancy. In the search for Ets factors involved in mammary gland development and malignancy, ESX was found to be upregulated in a subset of breast tumours and cell lines. We report the transcriptional regulation of ESX in epithelial breast cancer cells. Transient reporter assays using the ESX promoter show that ESX transcription is regulated by ErbB receptor signalling. In cell lines and in 45 primary ductal breast cancers we show that ESX transcript expression significantly correlates with ErbB2 transcript levels. Moreover, expression of ErbB2 in cells upregulates ESX promoter activity while inhibition of ErbB2 or its downstream signaling pathways decrease both ESX promoter activity and endogenous ESX protein levels. These results indicate that the ESX promoter represents a transcriptional target of ErbB2, and ESX expression may represent a downstream mediator of ErbB2 signaling and ErbB2-induced gene expression.
Neve
Richard M
RM
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Ylstra
Bauke
B
Chang
Chuan-Hsiung
CH
Albertson
Donna G
DG
Benz
Christopher C
CC
D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C105529:ELF3 protein, human