The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP9 in the stroma of pre-invasive breast cancer

The first steps of stroma generation are of pivotal importance for carcinog enesis because at this stage are initiated both angiogenesis, the prerequis ite for continuous tumour growth, and the proliferation of stromal fibrobla sts, These developments contribute to the onset of tumour invasion by secre ting several matrix-degrading proteases, Both angiogenesis and the producti on of proteases are tightly controlled at several levels; of significant im portance is transcription, The Ets-1 transcription factor transactivates se veral genes encoding matrix-degrading proteases and is thought to be involv ed in both tumour vascularization and invasion. This study therefore invest igated, by in situ hybridization and immunohistochemistry, the expression o f Ets-1 and of two of its target genes, encoding matrix metalloproteinase ( MMP) 1 and MMP9, in order to demonstrate a topographical in vivo correlatio n between the expression of these three genes during breast cancer formatio n. All three genes were first expressed within both endothelial cells and s tromal fibroblasts during the onset of stroma generation around intraductal and intralobular in situ carcinomas and they mere significantly up-regulat ed in the stroma of invasive ductal and lobular canters. The results of thi s study further support the suggested in vivo role of Ets-1 for both angiog enesis and tumour invasion, via matrix-degrading proteases which are alread y expressed during the early stages of breast carcinogenesis. Copyright (C) 2001 John Wiley & Sons, Ltd.