PANCREATIC NEOPLASIA INDUCED BY SV40 T-ANTIGEN EXPRESSION IN ACINAR-CELLS OF TRANSGENIC MICE
PANCREATIC NEOPLASIA INDUCED BY SV40 T-ANTIGEN EXPRESSION IN ACINAR-CELLS OF TRANSGENIC MICE
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DOI：
10.1126/science.2821617
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发表时间：
1987-10-09
期刊：
影响因子：
56.9
通讯作者：
BRINSTER, RL
中科院分区：
文献类型：
--
作者：
ORNITZ, DM;HAMMER, RE;BRINSTER, RL
产生了三个系的转基因小鼠，其由于腺泡细胞中弹性蛋白酶I-SV 40 T-抗原融合基因的表达而发生胰腺肿瘤。发育分析表明，这种疾病的个体发育至少有两个阶段的过程。第一阶段是T抗原诱导的癌前状态，其特征是胰腺外分泌从增生进展到发育不良，四倍体细胞百分比增加，腺泡细胞分化停滞。第二阶段的特征是形成似乎是单克隆的肿瘤结节，因为它们具有离散的非整倍体DNA含量。与正常胰腺组织相比，结节内的细胞具有少5倍的总RNA，少约50倍的胰腺特异性信使RNA，以及增加的T抗原信使RNA水平。已经衍生出保留胰腺和肿瘤性质的肿瘤细胞系。
Three lines of transgenic mice were produced that develop pancreatic neoplasms as a consequence of expression of an elastase I-SV40 T-antigen fusion gene in the acinar cells. A developmental analysis suggests at least two-stage process in the ontogeny of this disease. The first stage is a T antigen-induced, preneoplastic state characterized by a progression from hyperplasia to dysplasia of the exocrine pancreas, by an increased percentage of tetraploid cells, and by an arrest in acinar cell differentiation. The second stage is characterized by the formation of tumor nodules that appear to be monoclonal, because they have discrete aneuploid DNA contents. The cells within the nodules as compared to normal pancreatic tissue have less total RNA by a factor of 5, less pancreas-specific messenger RNA by a factor of about 50, and increased levels of T-antigen messenger RNA. A tumor cell line has been derived that retains both pancreatic and neoplastic properties.