Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer.
Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer.
复制标题
DOI：
10.1371/journal.pone.0020687
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wellstein A
中科院分区：
文献类型：
--
作者：
LaConti JJ;Shivapurkar N;Preet A;Deslattes Mays A;Peran I;Kim SE;Marshall JL;Riegel AT;Wellstein A
microRNA（miRs）调节mRNA和蛋白质的表达水平，因此可以促进癌症的发生和发展。除了细胞内功能外，miR还从细胞中释放并进入循环。我们推测，循环miR可以提供对癌症进展期间改变的途径的洞察，并可能指示对治疗的反应。在这里，我们关注胰腺癌的恶性进展。我们报道了在p48-Cre/LSL-KrasG 12 D小鼠模型中，在正常组织向浸润性胰腺癌进展过程中miR表达模式的变化反映了在人胰腺癌组织中观察到的miR变化。在小鼠模型中，当比较正常组织、癌前病变和浸润性癌时，发现miR-148 a/B和miR-375表达降低，而miR-10、miR-21、miR-100和miR-155表达增加。发现预测的靶mRNA FGFR 1（miR-10）和MLH 1（miR-155）下调。患者血浆样本中9种microRNA的定量可将胰腺癌与其他癌症以及非癌性胰腺疾病区分开来。最后，吉西他滨治疗对照动物和胰腺癌p48-Cre/LSL-KrasG 12 D动物引起循环miR的明显和高达60倍的变化，表明对正常和癌组织的不同药物作用。这些发现支持了在循环中检测miR的重要性，并表明循环miR可以作为药物反应的指标。
microRNAs (miRs) modulate the expression levels of mRNAs and proteins and can thus contribute to cancer initiation and progression. In addition to their intracelluar function, miRs are released from cells and shed into the circulation. We postulated that circulating miRs could provide insight into pathways altered during cancer progression and may indicate responses to treatment. Here we focus on pancreatic cancer malignant progression. We report that changes in miR expression patterns during progression of normal tissues to invasive pancreatic adenocarcinoma in the p48-Cre/LSL-KrasG12D mouse model mirrors the miR changes observed in human pancreatic cancer tissues. miR-148a/b and miR-375 expression were found decreased whereas miR-10, miR-21, miR-100 and miR-155 were increased when comparing normal tissues, premalignant lesions and invasive carcinoma in the mouse model. Predicted target mRNAs FGFR1 (miR-10) and MLH1 (miR-155) were found downregulated. Quantitation of nine microRNAs in plasma samples from patients distinguished pancreatic cancers from other cancers as well as non-cancerous pancreatic disease. Finally, gemcitabine treatment of control animals and p48-Cre/LSL-KrasG12D animals with pancreatic cancer caused distinct and up to 60-fold changes in circulating miRs that indicate differential drug effects on normal and cancer tissues. These findings support the significance of detecting miRs in the circulation and suggests that circulating miRs could serve as indicators of drug response.
登录
查看更多内容
影响因子：
3.5
作者：
Grützmann, R;Foerder, M;Pilarsky, C
通讯作者：
Pilarsky, C
影响因子：
3.6
作者：
Habbe, Nils;Koorstra, Jan-Bart M.;Maitra, Anirban
通讯作者：
Maitra, Anirban
DOI：
10.1073/pnas.0701117104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Carriere, Catherine;Seeley, Elliott S.;Korc, Murray
通讯作者：
Korc, Murray
影响因子：
6.9
作者：
Golde, WT;Gollobin, P;Rodriguez, LL
通讯作者：
Rodriguez, LL
影响因子：
50.3
作者：
Hingorani, SR;Wang, LF;Tuveson, DA
通讯作者：
Tuveson, DA