Role of the 21-kDa protein TIMP-3 in oncogenic transformation of cultured chicken embryo fibroblasts
Autor: | Susan P. Hawkes, Te-Tuan Yang |
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Rok vydání: | 1992 |
Předmět: |
Chick Embryo
Matrix metalloproteinase Biology Models Biological Histones Extracellular matrix chemistry.chemical_compound Complementary DNA Cell Adhesion medicine Animals Fibroblast Peptide sequence Cells Cultured Tissue Inhibitor of Metalloproteinase-3 Metalloproteinase Multidisciplinary Metalloendopeptidases Fibroblasts Molecular biology Extracellular Matrix Neoplasm Proteins Molecular Weight Cell Transformation Neoplastic medicine.anatomical_structure chemistry Cell culture Phorbol Tetradecanoylphorbol Acetate Cell Division Research Article |
Zdroj: | Proceedings of the National Academy of Sciences. 89:10676-10680 |
ISSN: | 1091-6490 0027-8424 |
Popis: | The 21-kDa protein is an extracellular matrix (ECM) component whose synthesis is stimulated transiently during oncogenic transformation of chicken embryo fibroblasts (CEF) or after treatment of normal cells with the tumor promoter phorbol 12-myristate 13-acetate. Biochemical characterization indicates that the protein is related, but not identical, to two members of the family of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. The cDNA of the 21-kDa protein was recently cloned, and based upon its deduced amino acid sequence and other supporting data we propose that it is another member of this family, a TIMP-3. We now report electrophoretic purification of sufficient quantities of this protein to determine its function. The protein promotes the detachment of transforming cells from the ECM. Although its presence in the matrix may be necessary for cell release it is not the only factor involved because it does not influence the adhesive properties of nontransformed cells. It also appears to accelerate the morphological changes associated with cell transformation and stimulates the proliferation of growth-retarded, nontransformed cells maintained under low serum conditions. Based on these data we hypothesize that the 21-kDa protein promotes the development of the transformed phenotype in cultured cells. |
Databáze: | OpenAIRE |
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