THE PROTOONCOGENE INT-1 ENCODES A SECRETED PROTEIN ASSOCIATED WITH THE EXTRACELLULAR-MATRIX
THE PROTOONCOGENE INT-1 ENCODES A SECRETED PROTEIN ASSOCIATED WITH THE EXTRACELLULAR-MATRIX
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DOI：
10.1002/j.1460-2075.1990.tb08276.x
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发表时间：
1990-05-01
期刊：
影响因子：
11.4
通讯作者：
BROWN, AMC
中科院分区：
文献类型：
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作者：
BRADLEY, RS;BROWN, AMC
当原癌基因int-1被小鼠乳腺肿瘤病毒的前病毒插入激活时，在乳腺肿瘤发生中起重要作用。在正常小鼠组织中，该基因在胚胎神经管中表达，表明其具有发育功能，而在果蝇中，int-1的同源基因是无翅的片段极性基因。为了研究int-1的蛋白产物，我们获得了被表达int-1 cDNA的多拷贝逆转录病毒载体感染的成纤维细胞系。通过Western blot分析和免疫沉淀，我们鉴定出了从这些细胞分泌的一种44 kd形式的int-1蛋白。从其在sds -聚丙烯酰胺凝胶中较慢的迁移和在脉冲追逐实验中较长的半衰期判断，44 kd物种不同于主要的细胞内形式的int-1蛋白。在正常生长条件下，在细胞培养基中很少或根本检测不到44kd蛋白，而是发现大多数与细胞外基质（ECM）相关。该蛋白在体外似乎与肝素结合，表明它可能与ECM中的糖胺多糖结合。这些数据支持了int-1蛋白可能在细胞间短距离通讯中发挥作用的观点。
The proto-oncogene int-1 plays an important role in mammary tumorigenesis when activated by proviral insertions of the mouse mammary tumor virus. In normal mouse tissues the gene is expressed in the embryonic neural tube, suggesting a developmental function, while in Drosophila the homolog of int-1 is the segment polarity gene wingless. In order to study the protein products of int-1 we have derived fibroblast cell lines infected with multiple copies of a retroviral vector expressing int-1 cDNA. By Western blot analysis and immunoprecipitation we have identified a 44 kd form of int-1 protein which is secreted from these cells. The 44 kd species is distinct from the major intracellular forms of int-1 protein as judged by its slower mobility in SDS-polyacrylamide gels and by its longer half-life in pulse-chase experiments. Under normal growth conditions, little or none of the 44 kd protein is detectable in the cell culture medium but instead the majority is found associated with the extracellular matrix (ECM). The protein appears to bind heparin in vitro, suggesting that it might bind glycosaminglycans in the ECM. These data support the view that int-1 protein may play a role in cell-cell communication over short distances.