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, are required for transcriptional regulation of viral and cellular promoters in infected and transfected culture cells and for transformation of primary rodent cells. Here, we established a line of transgenic mice carrying the E1 region gene of human adenovirus type 12 under the control of the human renin promoter, in which a neuroectodermal tumor derived from retroperitoneal, olfactory, and/or pelvic regions was heritably developed with varying degrees of incidence and the phenotype was successfully passed through six generations. The transgenes were located in the region E2-E3 bands of chromosome 7 with which no genetic linkage to neuroectodermal tumors was previously demonstrated, and expressed only in the tumors but not in another tissue examined. Notably, in 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 the heritable formation of neuroectodermal tumors associated with co-expression of the three sets of myc family genes.
Sugiyama
F
F
Laboratory Research Animal Center, University of Tsukuba, Ibaraki, Japan.
Sagara
M
M
Matsuda
Y
Y
Horiguchi
H
H
Kamma
H
H
Ogata
T
T
Hatae
T
T
Yagami
K
K
Murakami
K
K
Fukamizu
A
A
D017498:Adenovirus E1 Proteins / Q000235:genetics*; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D005260:Female; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D016259:Genes, myc / Q000502:physiology; D005819:Genetic Markers; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D017599:Neuroectodermal Tumors / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis; D012083:Renin / Q000235:genetics*; D015533:Transcriptional Activation
D017498:Adenovirus E1 Proteins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers; D012313:RNA; D012083:Renin