BINDING OF FACTOR VIIA TO TISSUE FACTOR INDUCES ALTERATIONS IN GENE-EXPRESSION IN HUMAN FIBROBLAST CELLS - UP-REGULATION OF POLY(A) POLYMERASE

Tissue factor (TF) is the cellular receptor for an activated form of c lotting factor VII (VIIa) and the binding of factor VII(a) to TF initi ates the coagulation cascade. Sequence and structural patterns extract ed from a global alignment of TF confers homology with interferon rece ptors of the cytokine receptor super family, Several recent studies su ggested that TF could function as a genuine signal transducing recepto r, However, it is unknown which biological function(s) of cells are al tered upon the ligand, VIIa, binding to TF, In the present study, we e xamined the effect of VIIa binding to cell surface TF on cellular gene expression in fibroblasts. Differential mRNA display PCR technique wa s used to identify transcriptional changes in fibroblasts upon VIIa bi nding to TF, The display showed that VIIa binding to TF either up or d own-regulated several mRNA species, The differential expression of one such transcript, VIIa-induced up-regulation, was confirmed by Norther n blot analysis, Isolation of a full-length cDNA corresponding to the differentially expressed transcript revealed that VIIa up-regulated ge ne was poly(A) polymerase. Northern blot analysis of various carcinoma s and normal human tissues revealed an over expression of PAP in cance r tissues, Enhanced expression of PAP upon VIIa binding to tumor cell TF may potentially play an important role in tumor metastasis.