Preneoplastic lesions induced by myc and src oncogenes in reconstituted mouse bladder.

To define a role for different oncogenes in bladder neoplastic progression we have introduced viral myc and src oncogenes, singly or in combination, into intact normal urothelium. After incubation with virus, infected mucosa was heterotransplanted under the renal capsule of syngeneic animals and monitored for progression toward malignancy by use of histologic and immunofluorescence techniques. Although v-myc alone induced focal hyperplastic change, more dysplastic lesions were observed after expression of the src oncogene product in urothelial implants. In contrast, lesions induced by myc and src acting cooperatively were highly proliferative, displaying evidence of tumor formation within the 6-week study period. The presence and expression of myc and src oncogenic proteins, associated with preneoplastic and neoplastic lesions, was confirmed by use of Southern blot analysis and an immune complex kinase assay, respectively. These results indicate the formation of histologically distinct preneoplastic change elicited by the action of a single oncogene with induction of neoplastic changes when such oncogenic elements act cooperatively. This model provides an opportunity to study the action of different oncogenes throughout bladder neoplastic progression in vivo.