Neve Richard M, Ylstra Bauke, Chang Chuan-Hsiung, Albertson Donna G, Benz Christopher C
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Oncogene. 2002 May 30;21(24):3934-8. doi: 10.1038/sj.onc.1205503.
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.
Ets多基因家族的不同成员在发育、细胞分化、组织特异性基因表达和人类恶性肿瘤中发挥着不同的作用。在寻找参与乳腺发育和恶性肿瘤的Ets因子过程中，发现ESX在一部分乳腺肿瘤和细胞系中表达上调。我们报道了上皮性乳腺癌细胞中ESX的转录调控。使用ESX启动子的瞬时报告基因分析表明，ESX转录受ErbB受体信号传导调控。在细胞系和45例原发性导管乳腺癌中，我们发现ESX转录本表达与ErbB2转录水平显著相关。此外，细胞中ErbB2的表达上调ESX启动子活性，而抑制ErbB2或其下游信号通路则降低ESX启动子活性和内源性ESX蛋白水平。这些结果表明，ESX启动子是ErbB2的转录靶点，ESX表达可能代表ErbB2信号传导和ErbB2诱导基因表达的下游介质。
