Notch and Kras in pancreatic cancer: at the crossroads of mutation, differentiation and signaling.
Notch and Kras in pancreatic cancer: at the crossroads of mutation, differentiation and signaling.
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DOI：
10.4161/cc.8.12.8744
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Murtaugh LC
中科院分区：
文献类型：
--
作者：
De La O JP;Murtaugh LC
KRAS原癌基因的激活突变在胰腺导管腺癌（PDAC）及其假定的前体病变胰腺上皮内瘤变（PanIN）中几乎无处不在。激活Kras等位基因在小鼠胰腺中的条件表达产生了一个模型，该模型忠实地概括了PanIN的形成和PDAC的进展。重要的是，尽管这些小鼠胰腺中的几乎所有细胞都表达活化的Kras，但只有极少数细胞产生PanINs。Kras的转化活性如何在胰腺中受到限制尚不清楚，产生PanINs和PDAC的细胞类型也同样未知。在这里，我们描述了我们最近的研究结果，证明了腺泡细胞能够形成Kras诱导的PanINs，并且活性Notch信号可以在PanIN的启动和进展中与Kras协同作用。进一步了解Notch和Kras如何协同作用，以及确定其他胰腺细胞类型如何促进PDAC发展的实验，应该有助于开发这种癌症迫切需要的新疗法和早期检测技术。
Activating mutations in the KRAS proto-oncogene occur almost ubiquitously in pancreatic ductal adenocarcinoma (PDAC) and in its putative precursor lesions, pancreatic intraepithelial neoplasia (PanIN). Conditional expression of an activated Kras allele in the mouse pancreas produces a model that faithfully recapitulates PanIN formation and progression to PDAC. Importantly, although nearly every cell in the pancreata of these mice express activated Kras, only a very small minority of cells give rise to PanINs. How the transforming activity of Kras is constrained in the pancreas remains unknown, and the cell types from which PanINs and PDAC arise are similarly unknown. Here, we describe our recent results demonstrating that acinar cells are competent to form Kras-induced PanINs, and that active Notch signaling can synergize with Kras in PanIN initiation and progression. Further efforts to understand how Notch and Kras synergize, as well as experiments to determine how other pancreatic cell types contribute to PDAC development, should aid in the development of new therapies and early detection techniques that are desperately needed for this cancer.
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DOI：
10.1073/pnas.0810111105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Jean-Paul, De La O.;Emerson, Lyska L.;Murtaugh, L. Charles
通讯作者：
Murtaugh, L. Charles
DOI：
10.1073/pnas.0701117104
发表时间：
2007-03-13
影响因子：
11.1
作者：
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通讯作者：
Korc, Murray
DOI：
10.1016/s0022-5320(62)80028-8
发表时间：
1962-01-01
期刊：
JOURNAL OF ULTRASTRUCTURE RESEARCH
影响因子：
--
作者：
EKHOLM, R;EDLUND, Y;ZELANDER, T
通讯作者：
ZELANDER, T
DOI：
10.1073/pnas.0810097105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Habbe, Nils;Shi, Guanglu;Maitra, Anirban
通讯作者：
Maitra, Anirban
影响因子：
29.4
作者：
Jensen, JN;Cameron, E;Jensen, J
通讯作者：
Jensen, J