DBL EXPRESSION DRIVEN BY THE NEURON-SPECIFIC ENOLASE PROMOTER INDUCESTUMOR-FORMATION IN TRANSGENIC MICE WITH A P53(+ -) GENETIC BACKGROUND/

The dbl oncogene, generated by the truncation of the amino-terminal po rtion of the proto-oncogene sequence, encodes a guanine-nucleotide-rel easing factor. The transforming activity of this oncogene has never be en demonstrated in vivo or in vitro except in the NIH 3T3 mouse fibrob last cell line. The expression of the proto-dbl transcript is confined to tissues and tumors of neuroectodermal derivation. Therefore, to st udy the transforming activity of the dbl oncogene in vivo. we have gen erated transgenic mice that express this oncogene in neuroepithelial t issues. Mice carrying the dbl oncogene did not develop a tumor. Succes sively, to establish whether dbl interacts with the tumor suppressor g ene p53 in tumorigenesis, we have used a p53 deficient mouse strain. T he results reported here indicate that dbl is capable of causing tumor formation in vivo when its expression is driven in an appropriate cel lular and genetic environment. (C) 1995 Academic Press, Inc.