Down-regulated proteins of mesenchymal tumor cells.
To identify proteins that are lost during the establishment of the transformed phenotype of a tumor cell, we have prepared a subtracted cDNA library with mRNA from normal human fibroblasts and from their matched SV40 transformed counterparts. More than 40 clones were obtained that showed a dramatic reduction in their relative expression after oncogenic transformation. The proteins encoded by these clones could be grouped into four distinct classes: extracellular matrix proteins (fibronectin, beta ig-h3, collagen VI), enzymes (collagenase, urokinase), cytoskeletal proteins (vinculin, SM22) and regulatory proteins (beta-glycan, integrin-associated protein, myosin kinase, IGFBP-5). Six novel gene products were discovered during these experiments, including a novel serine protease, a zyxin-like protein, an ankyrin-like protein and a GTP-binding protein. Only four of all the transformation-sensitive cDNAs were consistently down-regulated when a variety of cell lines derived 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.
Schenker
T
T
MEM-Institute, University of Bern, Switzerland.
Trueb
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004798:Enzymes / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008637:Mesenchymoma / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D004798:Enzymes; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger