The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia
The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia
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DOI：
10.1073/pnas.0701117104
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发表时间：
2007-03-13
影响因子：
11.1
通讯作者：
Korc, Murray
中科院分区：
文献类型：
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作者：
Carriere, Catherine;Seeley, Elliott S.;Korc, Murray
为了确定胰腺导管腺癌（PDAC）中初始致癌突变发生的细胞区室，我们建立了一个小鼠模型，在该模型中，突变Kras （Kras (G12D)）的内源性表达最初指向以Nestin表达为特征的胰腺外分泌祖细胞群。将致癌Kras靶向这种受限的细胞室足以形成胰腺上皮内瘤变（PanINs），这是PDAC的假定前体。PanINs出现的级别和频率与KraSG12D通过pdx1驱动的Cre重组酶策略靶向整个胰腺时相同。因此，Nestin细胞系对Kras的致癌激活反应高度敏感，可能代表了PDAC产生的难以捉摸的祖细胞群。
To determine the cell compartment in which initial oncogenic mutations occur in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (KraS(G12D)) was initially directed to a population of pancreatic exocrine progenitors characterized by the expression of Nestin. Targeting of oncogenic Kras to such a restricted cell compartment was sufficient for the formation of pancreatic intra-epithelial neoplasias (PanINs), putative precursors to PDAC. PanINs appeared with the same grade and frequency as observed when KraSG12D was targeted to the whole pancreas by a Pdx1-driven Cre recombinase strategy. Thus, the Nestin cell lineage is highly responsive to Kras oncogenic activation and may represent the elusive progenitor population in which PDAC arises.