SEQUENCE OF THE HUMAN INVASION-INDUCING TIAM1 GENE, ITS CONSERVATION IN EVOLUTION AND ITS EXPRESSION IN TUMOR-CELL LINES OF DIFFERENT TISSUE ORIGIN

By means of proviral tagging in combination with in vitro selection fo r invasive T-lymphoma variants, we have previously identified the muri ne invasion- and metastasis-inducing Tiam1 gene. Tiam1 encodes a novel protein which shares a Dbl-homology (DH) domain with GDP dissociation stimulator-(GDS) proteins that activate Rho-like GTPases, We have clo ned the human TIAM1 coding sequence and studied its evolutionary conse rvation and expression pattern, TIAM1 is highly conserved among verteb rates, The close similarity between human T1AM1 and the mouse homologu e is indicated by 88% and 95% identity of nucleotides and predicted se quences, respectively, The murine gene is highly expressed in brain an d testis and at low or moderate levels in almost all other normal tiss ues, Interestingly, Tiam1 transcripts were found in virtually all anal ysed tumor cell lines of human and rodent origin including B- and T-ly mphomas, neuroblastomas, melanomas and carcinomas, The evolutionary co nservation as well as the broad expression pattern of Tiam1 in most no rmal tissues, suggests a general function in cellular signaling proces ses presumably by activation of a Rho-like GTPase that regulates the c ytoskeletal organization.