Increased expression of DNA repair genes in invasive human pancreatic cancer cells.
Increased expression of DNA repair genes in invasive human pancreatic cancer cells.
复制标题
DOI：
10.1097/mpa.0b013e31821ae25b
复制
发表时间：
2011-07
期刊：
影响因子：
2.9
通讯作者：
Farrar WL
中科院分区：
文献类型：
--
作者：
Mathews LA;Cabarcas SM;Hurt EM;Zhang X;Jaffee EM;Farrar WL
胰腺癌是2009年美国癌症死亡的第四大原因。肿瘤切除后的复发是由于肿瘤细胞的存活。为了更好地了解这些高度侵袭性的细胞，进行了基因表达微阵列。使用建立的系HPAC和PANC 1和Matrigel测定，进行基因组表达阵列以分析侵袭性细胞和总细胞之间的模式。观察到与DNA修复相关的基因的表达显著增加。当将大量细胞与推定的肿瘤起始细胞（TIC）群体进行比较时，许多相同的基因也表现出表达的增加。使用球状体技术分离TIC群体，并且与散装细胞相比，球状体细胞在用药物吉西他滨攻击后更快地功能性修复DNA中的断裂。最后，使用Oncomine，我们观察到与从原发部位分离的组织相比，从转移性胰腺癌分离的组织中BRCA 1和RAD 51的DNA拷贝数显著增加。从这些数据中，我们得出结论，胰腺肿瘤中最具侵袭性的细胞由于其基因组稳定性增加而能够茁壮成长。这些细胞也与肿瘤中的TIC群体相关。
Pancreatic cancer was the fourth leading cause of cancer death in the United States in 2009. Recurrence of disease following resection occurs due to neoplastic cell survival. To better understand these highly aggressive cells, gene expression microarrays were performed. Using the established lines HPAC and PANC1 and a Matrigel assay, genome expression arrays were performed to analyze patterns between invasive and total cells. Significant increases in the expression of genes related to DNA repair were observed. A number of the same genes also demonstrated an increase in expression when comparing bulk cells to a putative tumor initiating cell (TIC) population. The TIC population was isolated using the spheroid technique, and compared to bulk cells, spheroid cells functionally repair breaks in DNA faster after challenged with the drug gemcitabine. Finally, using Oncomine, we observed a significant increase in DNA copy number of BRCA1 and RAD51 in tissue isolated from metastatic pancreatic cancer compared to tissue isolated from the primary site. From these data we conclude that the most invasive cells within a pancreatic tumor are able to thrive due to their increased genomic stability. These cells have also been linked to the TIC population in a tumor.