Gene expression and protein deposition of major basement membrane components and TGF-beta 1 in human breast cancer

In the present study we used immunohistochemistry and in-situ hybridization for the localization of major basement membrane (BM) components and their mRNA, respectively, in order to determine the extent of BM production and deposition in normal mammary tissue as well as in invasive mamma carcinomas. While normal mammary tissue showed an intact epithelial BM, as evidenced by a continuous linear staining for collagen i.v., laminin, heparan sulfate proteoglycan (perlecan) and fibronectin, this staining was widely lost in the invasive carcinomas. Non-invasive intraductal areas of the carcinomas (carcinoma-in-situ) revealed focal fragmentation and duplication of the epithelial BM. Using in-situ hybridization, we observed only focally positive mRNA-expression for collagen i.v.-, perlecan- and fibronectin-mRNA in normal glands, while mRNA-signals were significantly enhanced in one case of fibroadenoma and particularly in invasive and non-invasive carcinomas, regardless of the degree of tumor cell differentiation. In these instances both tumor and stroma cells were positively labelled. In addition, we could demonstrate a significant increase in the level of TGF-beta 1-mRNA--as the most active cytokine for the induction of matrix component production--by carcinoma cells and to lesser extent by stroma cells. The discrepancy between significantly enhanced mRNA-synthesis and loss in protein deposition points either to an upregulated activity of matrix degrading proteinases (matrix-metalloproteinases) or a posttranslational block of protein synthesis or both.