Pendurthi U R, Alok D, Rao L V
Department of Biochemistry, University of Texas Health Center, Tyler, TX 75710, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12598-603. doi: 10.1073/pnas.94.23.12598.
Tissue factor (TF) is the cellular receptor for an activated form of clotting factor VII (VIIa) and the binding of factor VII(a) to TF initiates the coagulation cascade. Sequence and structural patterns extracted from a global alignment of TF confers homology with interferon receptors of the cytokine receptor super family. Several recent studies suggested that TF could function as a genuine signal transducing receptor. However, it is unknown which biological function(s) of cells are altered upon the ligand, VIIa, binding to TF. In the present study, we examined the effect of VIIa binding to cell surface TF on cellular gene expression in fibroblasts. Differential mRNA display PCR technique was used to identify transcriptional changes in fibroblasts upon VIIa binding to TF. The display showed that VIIa binding to TF either up or down-regulated several mRNA species. The differential expression of one such transcript, VIIa-induced up-regulation, was confirmed by Northern blot analysis. Isolation of a full-length cDNA corresponding to the differentially expressed transcript revealed that VIIa-up-regulated gene was poly(A) polymerase. Northern blot analysis of various carcinomas and normal human tissues revealed an over expression of PAP in cancer tissues. Enhanced expression of PAP upon VIIa binding to tumor cell TF may potentially play an important role in tumor metastasis.
组织因子（TF）是凝血因子VII（VIIa）活化形式的细胞受体，VII（a）因子与TF的结合启动凝血级联反应。从TF的全局比对中提取的序列和结构模式赋予其与细胞因子受体超家族的干扰素受体同源性。最近的几项研究表明，TF可能作为一种真正的信号转导受体发挥作用。然而，尚不清楚配体VIIa与TF结合后细胞的哪些生物学功能会发生改变。在本研究中，我们检测了VIIa与细胞表面TF结合对成纤维细胞中细胞基因表达的影响。采用差异mRNA显示PCR技术来鉴定VIIa与TF结合后成纤维细胞中的转录变化。结果显示，VIIa与TF结合会使几种mRNA种类上调或下调。通过Northern印迹分析证实了其中一种转录本（VIIa诱导的上调）的差异表达。对差异表达转录本对应的全长cDNA进行分离，结果显示VIIa上调的基因是聚腺苷酸聚合酶（PAP）。对各种癌组织和正常人体组织进行Northern印迹分析发现，PAP在癌组织中过表达。VIIa与肿瘤细胞TF结合后PAP表达增强可能在肿瘤转移中发挥重要作用。
