RUNX3 expression in primary and metastatic pancreatic cancer
RUNX3 expression in primary and metastatic pancreatic cancer
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DOI：
10.1136/jcp.2003.013011
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Friess, H
中科院分区：
文献类型：
--
作者：
Li, J;Kleeff, J;Friess, H
目的：Runx转录因子是谱系特异性基因表达、细胞增殖和分化的重要调控因子。Runx3在大部分胃癌中表达缺失，提示在这种恶性肿瘤中具有肿瘤抑制作用。本研究探讨Runx3在胰腺组织中的表达和定位。方法：采用定量聚合酶链反应检测Runx3 mRNA。采用免疫组化方法定位Runx3在正常胰腺组织、原发性和转移性胰腺导管腺癌（PDAC）中的表达。分析了基础生长因子和转化生长因子β 1 （tgfβ 1）诱导的Runx3在培养的胰腺癌细胞系中的表达。结果：Runx3在正常胰腺组织中表达低至缺失，而在三分之一的癌组织中表达升高。Runx3仅存在于正常胰腺的胰岛中，而在胰腺癌中，在分析的24个样本中的7个样本的癌细胞中检测到Runx3。在16例淋巴细胞浸润的病例中，有6例在淋巴细胞中表达。在胰腺癌细胞系中，在Colo-357和T3M4细胞中存在Runx3 mRNA，但在其他细胞系中含量较低或不存在。TGFb1抑制Colo-357细胞中Runx3 mRNA的表达，对其他胰腺癌细胞系中Runx3的表达无影响。结论：正常胰腺中Runx3的表达仅限于胰岛。相比之下，相当比例的胰腺肿瘤表达Runx3，其表达局限于肿瘤细胞和浸润淋巴细胞。因此，Runx3可能在PDAC的发病机制中发挥作用。
Aim: Runx transcription factors are important regulators of lineage specific gene expression, cell proliferation, and differentiation. Runx3 expression is lost in a high proportion of gastric cancers, suggesting a tumour suppressive role in this malignancy. This study investigates the expression and localisation of Runx3 in pancreatic tissues.Methods: Quantitative polymerase chain reaction was used to measure Runx3 mRNA. Immunohistochemistry was carried out to localise Runx3 in normal pancreatic tissues, and in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Basal and transforming growth factor beta1 (TGFbeta1) induced Runx3 expression was analysed in cultured pancreatic cancer cell lines.Results: Runx3 expression was low to absent in normal pancreatic tissues, but increased in a third of cancer tissues. Runx3 was present only in islets in normal pancreas, whereas in pancreatic cancers, Runx3 was detected in the cancer cells of seven of 24 samples analysed. In addition, it was expressed by lymphocytes in six of the 16 cases with lymphocyte infiltration. In pancreatic cancer cell lines, Runx3 mRNA was present in Colo-357 and T3M4 cells, but was low to absent in the other cell lines tested. TGFb1 repressed Runx3 mRNA expressed in Colo-357 cells, and had no effect on Runx3 expression in the other pancreatic cancer cell lines.Conclusion: Runx3 expression is restricted to islets in the normal pancreas. In contrast, a considerable proportion of pancreatic tumours express Runx3, and its expression is localised in the tumour cells and in the infiltrating lymphocytes. Thus, Runx3 might play a role in the pathogenesis of PDAC.