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首页> 外文期刊>Cancer Cell >Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse.
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Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse.

机译：浸润前和浸润性导管胰腺癌及其在小鼠中的早期检测。

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To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients.
机译：为了评估致癌RAS突变在胰腺肿瘤发生中的作用，我们将内源性表达KRAS（G12D）定向到小鼠胰腺祖细胞。我们发现，生理水平的Kras（G12D）诱导导管病变，概括了人类胰腺上皮内瘤样变（PanINs）的全谱，这是浸润性胰腺癌的推定前体。 PanINs高度增殖，显示组织学进展的证据，并激活通常在导管上皮中处于静止状态的信号传导途径，表明潜在的治疗和化学预防目标可用于同类人类疾病。在低频时，这些病变也会自发发展为浸润性和转移性腺癌，从而将PanINs确立为浸润性疾病的明确前体。最后，具有PanINs的小鼠具有可识别的血清蛋白质组学特征，提示了一种检测患者侵袭前状态的方法。

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