HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma.
HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma.
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DOI：
10.1038/modpathol.2009.139
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发表时间：
2010-01
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影响因子：
--
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中科院分区：
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尽管胰腺导管腺癌是一种常见且几乎一致致命的癌症，但人们对导致肿瘤进展的分子事件知之甚少。高迁移率A1 （HMGA1）蛋白是一种建筑转录因子，与多种人类癌症的发病和进展有关，包括胰腺导管腺癌。在这里，我们研究了HMGA1在胰腺导管腺癌细胞系和手术切除肿瘤中的表达，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，我们检测了培养的胰腺导管腺癌细胞系中HMGA1a mRNA的水平，发现与正常胰腺组织相比，所有癌细胞中的HMGA1a mRNA水平都有所增加。为了研究HMGA1在原发性人类肿瘤中的作用，我们对125例胰腺腺癌和99例前体病变进行了免疫组织化学分析（PanIN 1-3）。我们在98%的胰腺腺癌病例中发现HMGA1的核染色，但只有43%的PanIN前体病变病例。此外，HMGA1免疫反应性与生存率降低、肿瘤进展和PanIN分级呈正相关。这些结果表明HMGA1促进胰腺导管腺癌的肿瘤进展，可能成为晚期疾病有用的生物标志物和合理的治疗靶点。
Although pancreatic ductal adenocarcinoma is a common and almost uniformly fatal cancer, little is known about the molecular events that lead to tumor progression. The high-mobility group A1 (HMGA1) protein is an architectural transcription factor that has been implicated in the pathogenesis and progression of diverse human cancers, including pancreatic ductal adenocarcinoma. Here, we investigated HMGA1 expression in pancreatic ductal adenocarcinoma cell lines and surgically resected tumors to determine if it could be a marker for more advanced disease. By real-time quantitative RT-PCR, we measured HMGA1a mRNA in cultured pancreatic ductal adenocarcinoma cell lines and found increased levels in all cancer cells compared to normal pancreatic tissue. To investigate HMGA1 in primary human tumors, we performed immunohistochemical analysis of 125 cases of pancreatic adenocarcinoma and 99 precursor lesions (PanIN 1–3). We found nuclear staining for HMGA1 in 98% of cases of pancreatic adenocarcinoma, but only 43% of cases of PanIN precursor lesions. Moreover, HMGA1 immunoreactivity correlates positively with decreased survival and advanced tumor and PanIN grade. These results suggest that HMGA1 promotes tumor progression in pancreatic ductal adenocarcinoma and could be a useful biomarker and rational therapeutic target in advanced disease.
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影响因子：
11.2
作者：
Tesfaye, Abeba;Di Cello, Francescopaolo;Resar, Linda M. S.
通讯作者：
Resar, Linda M. S.
影响因子：
11.2
作者：
Liau, Siong-Seng;Jazag, Amarsanaa;Whang, Edward E.
通讯作者：
Whang, Edward E.
影响因子：
6
作者：
van Heek, NT;Meeker, AK;Maitra, A
通讯作者：
Maitra, A
影响因子：
11.2
作者：
Hillion J;Dhara S;Sumter TF;Mukherjee M;Di Cello F;Belton A;Turkson J;Jaganathan S;Cheng L;Ye Z;Jove R;Aplan P;Lin YW;Wertzler K;Reeves R;Elbahlouh O;Kowalski J;Bhattacharya R;Resar LM
通讯作者：
Resar LM
影响因子：
6.2
作者：
Liau SS;Rocha F;Matros E;Redston M;Whang E
通讯作者：
Whang E