Carcinogenesis of pancreatic adenocarcinoma: precursor lesions.
Carcinogenesis of pancreatic adenocarcinoma: precursor lesions.
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DOI：
10.3390/ijms141019731
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发表时间：
2013-09-30
影响因子：
5.6
通讯作者：
Silvestris N
中科院分区：
文献类型：
--
作者：
Gnoni A;Licchetta A;Scarpa A;Azzariti A;Brunetti AE;Simone G;Nardulli P;Santini D;Aieta M;Delcuratolo S;Silvestris N
胰腺腺癌表现出多种分子变化，这些变化随着时间的推移呈指数级演变，导致癌细胞不仅能够存活，而且还能侵入周围组织并转移到远处。这些变化包括：癌基因和抑癌基因的遗传改变；细胞周期和导致细胞凋亡的途径的变化；以及上皮细胞向间质细胞转变的变化。最常见的改变涉及表皮生长因子受体 (EGFR) 基因、HER2 基因和 K-ras 基因。特别是，该肿瘤中已记录了肿瘤抑制基因功能的丧失，尤其是 CDKN2a、p53、DPC4 和 BRCA2 基因。然而，胰腺癌发病机制中涉及的其他分子事件有助于其发展和维持，特别是表观遗传事件。事实上，在胰腺腺癌中发挥作用的关键肿瘤抑制因子可能会通过高甲基化而改变，并且癌基因可以继发于允许的组蛋白修饰而上调。事实上，参与肿瘤侵袭性的因素可以通过失调的 microRNA 异常表达。这篇综述总结了目前对胰腺癌发生的了解，从正常细胞内发生胰腺癌直至扩散到远处器官。在这种情况下，强调这些分子改变可以为这种恶性肿瘤的早期诊断和新的有效疗法提供新的临床工具。
Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy.
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