ROLE OF THE 21-KDA PROTEIN TIMP-3 IN ONCOGENIC TRANSFORMATION OF CULTURED CHICKEN-EMBRYO FIBROBLASTS
ROLE OF THE 21-KDA PROTEIN TIMP-3 IN ONCOGENIC TRANSFORMATION OF CULTURED CHICKEN-EMBRYO FIBROBLASTS
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DOI：
10.1073/pnas.89.22.10676
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
HAWKES, SP
中科院分区：
文献类型：
--
作者：
YANG, TT;HAWKES, SP
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）的致瘤转化过程中或正常细胞用肿瘤启动子phorbol 12-肉豆蔻酸13-乙酸处理后受到短暂刺激。生化表征表明，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，但不完全相同。最近克隆了该蛋白的cDNA，根据其推断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，一个TIMP-3。我们现在报告电泳纯化足够数量的这种蛋白质，以确定其功能。这种蛋白质促进转化细胞脱离ECM。虽然它在基质中的存在可能是细胞释放所必需的，但它并不是唯一涉及的因素，因为它不影响未转化细胞的粘附特性。它似乎还能加速与细胞转化相关的形态变化，并刺激生长迟缓的、在低血清条件下维持的非转化细胞的增殖。基于这些数据，我们假设21 kda蛋白促进了培养细胞中转化表型的发展。
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.