SINGLE-STEP INDUCTION OF MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE BEARING THE ACTIVATED C-NEU ONCOGENE
SINGLE-STEP INDUCTION OF MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE BEARING THE ACTIVATED C-NEU ONCOGENE
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DOI：
10.1016/0092-8674(88)90184-5
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发表时间：
1988-07-01
期刊：
影响因子：
64.5
通讯作者：
LEDER, P
中科院分区：
文献类型：
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作者：
MULLER, WJ;SINN, E;LEDER, P
我们使用了携带由小鼠乳腺肿瘤病毒(MMTV)启动子驱动的c-neu癌基因的转基因小鼠来评估乳腺上皮癌变的逐步进展。与携带MMTV/c-myc或MMTV/v-Ha-ras癌基因的转基因小鼠随机发生孤立乳腺肿瘤不同，统一表达MMTV/c-neu基因的转基因小鼠患上乳腺癌，累及每个腺体的整个上皮。由于这些肿瘤是同步发生的，并且是多克隆起源的，激活的c-neu癌基因的表达似乎足以在一个步骤中诱导该组织的恶性转化。相反，c-neu转基因在腮腺或附睾处的表达导致良性的双侧上皮肥大和增生，在观察期内不会进展到完全恶变。这些结果表明，活化的癌基因和组织环境的组合是恶性进展的主要决定因素，c-neu活化形式在乳腺上皮中的表达具有特别有害的后果。
We have used transgenic mice that carry an activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV) promoter to assess the stepwise progression of carcinogenesis in mammary epithelium. Unlike the stochastic occurrence of solitary mammary tumors in transgenic mice bearing the MMTV/c-myc or the MMTV/v-Ha-ras oncogenes, transgenic mice uniformly expressing the MMTV/c-neu gene develop mammary adenocarcinomas that involve the entire epithelium in each gland. Because these tumors arise synchronously and are polyclonal in origin, expression of the activated c-neu oncogene appears to be sufficient to induce malignant transformation in this tissue in a single step. In contrast, expression of the c-neu transgene in the parotid gland or epididymis leads to benign, bilateral epithelial hypertrophy and hyperplasia which does not progress to full malignant transformation during the observation period. These results indicate that the combination of activated oncogene and tissue context are major determinants of malignant progression and that expression of the activated form of c-neu in the mammary epithelium has particularly deleterious consequences.