Fukamizu A, Sagara M, Sugiyama F, Horiguchi H, Kamma H, Hatae T, Ogata T, Yagami K, Murakami K
Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan.
J Biol Chem. 1994 Dec 9;269(49):31252-8.
Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transformation of primary cultured rodent cells. In order to investigate in vivo action of the E1 region, we established a line of transgenic mice carrying the oncogenic E1A and E1B genes of human adenovirus type 12 under control of the human angiotensinogen promoter. Histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying degrees of incidence. The transgene was expressed in the neuroectodermal tumors as well as in TNT-1 cells, a cell line established from the tumors, where the human angiotensinogen promoter was constitutively active. The high level expression of c-, L-, and N-myc without gene amplification was notable in the original tumors and TNT-1 cells, but not in another tissue examined. The co-expression of the three sets of myc family genes in both the original tumors and the established cell line provided the possibility that the target cells for transformation may belong to a specific cell type that expresses all these oncogenes during development.
腺病毒早期1（E1）区域基因产物，包括E1A和E1B，是原代培养的啮齿动物细胞转化所必需的。为了研究E1区域的体内作用，我们建立了一系列转基因小鼠，其携带人12型腺病毒的致癌E1A和E1B基因，并由人血管紧张素原启动子控制。组织病理学分析表明，转基因小鼠可遗传地发生起源于盆腔区域的神经外胚层肿瘤，发病率各不相同。转基因在神经外胚层肿瘤以及TNT-1细胞（一种从肿瘤建立的细胞系）中表达，在该细胞系中人血管紧张素原启动子持续活跃。在原始肿瘤和TNT-1细胞中，c-、L-和N-myc无基因扩增的高水平表达很显著，但在检查的其他组织中则不然。在原始肿瘤和建立的细胞系中三组myc家族基因的共表达提供了一种可能性，即转化的靶细胞可能属于在发育过程中表达所有这些致癌基因的特定细胞类型。
