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-site hybridiz ation for the localization of major basement membrane (BM) components and their mRNA, respectively, in order to determine the extent of BM p roduction and deposition in normal mammary tissue as well as in invasi ve mamma carcinomas. While normal mammary tissue showed an intact epit helial BM, as evidenced by a continous linear staining for collagen IV , laminin, heparan sulfate proteoglycan (perlecan) and fibronectin, th is staining was widely lost in the invasive carcinomas. Non-invasive i ntraductal areas of the carcinomas (carcinoma-in-situ) revealed focal fragmentation and duplication of the epithelial BM. Using in-situ hybr idization, we observed only focally positive mRNA-expression for colla gen IV-, perlecan- and fibronectin-mRNA in normal glands, while mRNA-s ignals were significantly enhanced in one case of fibroadenoma and par ticularly in invasive and non-invasive carcinomas, regardless of the d egree of tumor cell differentiation. In these instances both tumor and stroma cells were positively labelled. In addition we could demonstra te a significant increase in the level of TGF-beta 1-mRNA - as the mos t active cytokine for the induction of matrix component production - b y carcinoma cells and to lesser extent by stroma cells. The discrepanc y between significantly enhanced mRNA-synthesis and loss in protein de position points either to an upregulated activity of matrix degrading proteinases (matrix-metalloproteinases) or a posttranslational block o f protein synthesis or both.