Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice.
Preinvasive pancreatic neoplasia of ductal phenotype induced by acinar cell targeting of mutant Kras in transgenic mice.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
P. Grippo;Patrick S Nowlin;M. Demeure;D. Longnecker;E. Sandgren
中科院分区：
文献类型：
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作者：
P. Grippo;Patrick S Nowlin;M. Demeure;D. Longnecker;E. Sandgren
Kras癌基因的激活突变是最常见的，也许是最早的与胰腺癌相关的基因改变。为了研究Kras突变体与外分泌胰腺癌之间的联系，我们培育了携带弹性酶突变Kras基因的转基因小鼠，该基因靶向胰腺腺泡细胞表达。大多数弹性酶kras建立小鼠显示围产儿胰腺腺泡细胞增生和发育不良。然而，在两个幸存的谱系中，成年小鼠表现出浸润前胰腺肿瘤病变，具有导管形态，从而提供了一种独特的小鼠模型，其中病变组织类型和初始遗传改变与人类疾病重叠。我们的研究结果表明，Kras突变与胰腺早期导管样病变的发展有关，但附加的改变必须伴随着恶性肿瘤的进展。
Activating mutation of the Kras oncogene is the most frequent and perhaps the earliest genetic alteration associated with pancreatic cancer. To examine the link between mutant Kras and exocrine pancreatic cancer, we generated transgenic mice carrying an elastase-mutant Kras transgene, which targets expression to pancreatic acinar cells. Most elastase-Kras founder mice displayed perinatal pancreatic acinar cell hyperplasia and dysplasia. However, adult mice in two surviving lineages displayed preinvasive pancreatic neoplastic lesions with ductal morphology, thereby providing a unique mouse model in which lesion histotype and initiating genetic alteration overlap with the human disease. Our findings suggest that Kras mutation is associated with development of early stage duct-like lesions in pancreas, but that additional alterations must accompany progression to malignancy.