Microarray studies of factor VIIa-activated cancer cells.
Factor VIIa (FVIIa)-induced signal transduction is strongly dependent on cellular surface expression of Tissue Factor (TF) and Protease Activated Receptors (PARs). FVIIa signals primarily through PAR2. This contrasts to thrombin which signals primarily via PAR1 and does so without the assistance of a co-receptor, but by binding to an exosite on PAR1. Various TF:FVII-mediated cellular activities are now well documented and have indicated possible links to inflammation, atherosclerosis, angiogenesis, tissue repair, tumor growth and metastasis. Further knowledge about cellular responses induced by coagulation factors has been obtained by gene-expression profiling of MDA-MB-231 cells stimulated with FVIIa or alternatively with PAR1 or PAR2 agonist peptides. These studies and qPCR measurements of the transcription of selected genes in these and other carcinoma cell lines have provided new information about gene expression induced by PAR activation, the gene repertoire induced by TF:FVIIa via PAR2, and how it differs from that induced via PAR1 by thrombin.
Petersen
Lars Christian
LC
Haemostasis Biology, Novo Nordisk, Maalov, Denmark. LCP@novonordisk.com
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015942:Factor VIIa / Q000378:metabolism* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D040081:Protein Array Analysis; D044463:Receptor, PAR-1 / Q000819:agonists; D044464:Receptor, PAR-2 / Q000819:agonists; D015398:Signal Transduction; D013925:Thromboplastin / Q000378:metabolism
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D013925:Thromboplastin; D015942:Factor VIIa