Wagner H E, Steele G, Summerhayes I C
New England Deaconess Hospital, Department of Surgery, Boston, Mass 02115.
Surgery. 1990 Aug;108(2):146-52; discussion 152-3.
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.
为了确定不同癌基因在膀胱肿瘤进展中的作用，我们已将病毒myc和src癌基因单独或联合导入完整的正常尿路上皮。与病毒孵育后，将感染的黏膜异种移植到同基因动物的肾包膜下，并通过组织学和免疫荧光技术监测其向恶性肿瘤的进展。虽然单独的v-myc诱导了局灶性增生性改变，但在尿路上皮植入物中表达src癌基因产物后观察到了更多发育异常的病变。相比之下，myc和src协同作用诱导的病变具有高度增殖性，在6周的研究期内显示出肿瘤形成的迹象。分别使用Southern印迹分析和免疫复合物激酶测定法证实了与癌前和肿瘤病变相关的myc和src致癌蛋白的存在和表达。这些结果表明，单个癌基因的作用引发了组织学上不同的癌前改变，而当这些致癌元件协同作用时则诱导了肿瘤改变。该模型为研究不同癌基因在体内整个膀胱肿瘤进展过程中的作用提供了机会。
