HERITABLE FORMATION OF NEUROECTODERMAL TUMOR IN TRANSGENIC MICE CARRYING THE COMBINED E1 REGION GENE OF ADENOVIRUS-TYPE-12 WITH THE DEREGULATED HUMAN RENIN PROMOTER

Adenovirus early 1 (E1) region gene products, including E1A and E1B, a re required for transcriptional regulation of viral and cellular promo ters in infected and transfected culture cells and for transformation of primary rodent cells. Here, we established a line of transgenic mic e carrying the E1 region gene of human adenovirus type 12 under the co ntrol of the human renin promoter, in which a neuroectodermal tumor de rived from retroperitoneal, olfactory, and/or pelvic regions was herit ably developed with varying degrees of incidence and the phenotype was successfully passed through six generations. The transgenes were loca ted in the region E2-E3 bands of chromosome 7 with which no genetic li nkage to neuroectodermal tumors was previously demonstrated, and expre ssed only in the tumors but not in another tissue examined. Notably, i n addition to the expression of a neural marker gene N-CAM, the three nuclear oncogenes, c-, L-, and N-myc, were coexpressed in the tumors. These results suggest that E1A and E1B are cooperatively involved in t he heritable formation of neuroectodermal tumors associated with co-ex pression of the three sets of myc family genes. (C) 1995 Wile-Liss, In c.