HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma.
HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma.
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HMGA2蛋白表达与淋巴结转移相关，胰腺导管腺癌中的肿瘤等级增加。
DOI：
10.1038/modpathol.2008.140
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发表时间：
2009-01
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影响因子：
--
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中科院分区：
文献类型：
--
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胰腺导管腺癌是一种高度侵袭性、致死性的人类恶性肿瘤，一直未能成功治疗。尽管大多数患者存在转移性疾病，但肿瘤进展和转移的分子途径尚不清楚。高迁移率组A2 （HMGA2）蛋白是一种建筑转录因子，最近被认为与恶性肿瘤的发生和进展有关。在这里，我们检测了HMGA2基因在胰腺导管腺癌中的表达，以确定它是否可以作为更晚期疾病的标志。通过实时定量RT-PCR，我们发现与正常胰腺组织相比，三种培养的胰腺导管腺癌细胞系中有两种的HMGA2 mRNA显著增加。利用124例胰腺导管腺癌病例的组织微阵列，我们还通过免疫组织化学分析评估了HMGA2蛋白水平。我们发现HMGA2核免疫反应性与淋巴结转移和高肿瘤分级呈正相关。我们的研究结果支持HMGA2在胰腺导管腺癌进展中的作用，并表明它可能是一种有用的生物标志物和更晚期疾病的合理治疗靶点。
Pancreatic ductal adenocarcinoma is a highly aggressive, lethal human malignancy that continues to elude successful treatment. Although most patients present with metastatic disease, the molecular pathways that underlie tumor progression and metastases are poorly understood. The high mobility group A2 (HMGA2) protein is an architectural transcription factor that has recently been implicated in the development and progression of malignant tumors. Here, we examined HMGA2 gene expression in pancreatic ductal adenocarcinoma to determine if it could be a marker for more advanced disease. By real time quantitative RT-PCR, we showed a marked increase in HMGA2 mRNA in two of three cultured pancreatic ductal adenocarcinoma cell lines compared to normal pancreatic tissue. Using tissue microarrays generated from 124 pancreatic ductal adenocarcinoma cases, we also assessed HMGA2 protein levels by immunohistochemical analysis. We found that HMGA2 nuclear immunoreactivity correlates positively with lymph node metastases and high tumor grade. Our results support a role for HMGA2 in the progression of pancreatic ductal adenocarcinoma and suggest that it could be a useful biomarker and rational therapeutic target in more advanced disease.
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