Yang T T, Hawkes S P
Department of Pharmacy, University of California, San Francisco 94143-0446.
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10676-80. doi: 10.1073/pnas.89.22.10676.
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.
21 kDa蛋白是一种细胞外基质（ECM）成分，其合成在鸡胚成纤维细胞（CEF）致癌转化过程中或在用肿瘤启动子佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯处理正常细胞后会短暂受到刺激。生化特性表明，该蛋白与金属蛋白酶组织抑制剂家族的两个成员TIMP - 1和TIMP - 2相关，但并不相同。21 kDa蛋白的cDNA最近已被克隆，基于其推导的氨基酸序列和其他支持数据，我们提出它是该家族的另一个成员，即TIMP - 3。我们现在报告通过电泳纯化获得了足够量的这种蛋白以确定其功能。该蛋白促进转化细胞与细胞外基质分离。虽然它在基质中的存在可能是细胞释放所必需的，但它不是唯一涉及的因素，因为它不影响未转化细胞的黏附特性。它似乎还能加速与细胞转化相关的形态变化，并刺激在低血清条件下维持的生长迟缓的未转化细胞的增殖。基于这些数据，我们推测21 kDa蛋白促进培养细胞中转化表型的发展。
