Differentially expressed genes associated with the metastatic phenotype inbreast cancer

We have previously shown that human breast carcinoma cells demonstrating an interconverted phenotype, where keratin (epithelial marker) and vimentin ( mesenchymal marker) intermediate filaments are both expressed, have an incr eased ability to invade a basement membrane matrix in vitro. This increase in invasive potential has been demonstrated in MDA-MB-231 cells, which cons titutively express keratins and vimentin, and in MCF-7 cells transfected wi th the mouse vimentin gene (MoVi). However, vimentin expression alone is no t sufficient to confer the complete metastatic phenotype in MoVi cells, as determined by orthotopic administration. Thus, in the present study, differ ential display analysis was utilized to identify genes that are associated with the invasive and/or metastatic phenotype of several human breast cance r cell lines. Forty-four of 84 PCR fragments were differentially expressed as assessed by Northern hybridization analysis of RNA isolated from MCF-7, MoVi, and MB-231 cell lines. Polyadenylated RNA from a panel of poorly inva sive, invasive/non-metastatic, and invasive/metastatic breast carcinoma cel l lines was used to differentiate between cell-specific gene expression and genes associated with the invasive and/or metastatic phenotype(s). We obse rved that lysyl oxidase and a zinc finger transcription factor were express ed only in the invasive and/or metastatic cell line; whereas, a thiol-speci fic antioxidant and a heterochromatin protein were down-regulated in these cells. In contrast, tissue factor was expressed only in breast carcinoma ce ll lines having the highest invasive potential. These results suggest that specific genes involved in breast cancer invasion and metastasis can be sep arated by differential display methodology to elucidate the molecular basis of tumor cell progression.