DOWN-REGULATED PROTEINS OF MESENCHYMAL TUMOR-CELLS

To identify proteins that are lost during the establishment of the tra nsformed phenotype of a tumor cell, we have prepared a subtracted cDNA library with mRNA from normal human fibroblasts and from their matche d SV40 transformed counterparts. More than 40 clones were obtained tha t showed a dramatic reduction in their relative expression after oncog enic transformation. The proteins encoded by these clones could be gro uped into four distinct classes: extracellular matrix proteins (fibron ectin, beta ig-h8, collagen VI), enzymes (collagenase, urokinase), cyt oskeletal proteins (vinculin, SM22) and regulatory proteins (beta-glyc an, integrin-associated protein, myosin kinase, IGFBP-5). Six novel ge ne products were discovered during these experiments, including a nove l serine protease, a zyxin-like protein, an ankyrin-like protein, and a GTP-binding protein. Only four of all the transformation-sensitive c DNAs were consistently downregulated when a variety of cell lines deri ved from spontaneous mesenchymal tumors was investigated: beta ig-h3, collagen VI, the novel ankyrin-like protein, and IGFBP-5. It is likely that these gene products play an important role in the maintenance of the normal phenotype. (C) 1998 Academic Press.