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.