HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals
HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals
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DOI：
10.1002/ijc.22769
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发表时间：
2007-08-15
影响因子：
6.4
通讯作者：
Blok, Leen J.
中科院分区：
文献类型：
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作者：
Santegoets, Lindy A. M.;van Seters, Manon;Blok, Leen J.
外阴上皮内瘤变（VIN）是一种由人乳头瘤病毒引起的癌前病变。VIN的分子发病机制的基本知识是稀疏的。因此，我们通过使用全基因组的Affyssin Human U133 A plus 2基因芯片分析了9个VIN样品与10个对照样品的基因表达谱。结果通过实时定量RT-PCR分析和几个代表性基因（TACSTD 1，CCNE 2，AR和ESR 1）的免疫染色进行验证。微阵列（SAM）的显著性分析显示，与对照组相比，VIN中有1，497个基因差异表达。通过分析所观察到的差异影响的生物过程，我们发现VIN似乎是一种高度增殖性疾病;许多细胞周期蛋白（CCNA，CCNB和CCNE）和几乎所有的复制前复合物蛋白都上调。因此，VIN似乎不依赖于其增殖的旁分泌或内分泌信号。许多受体（例如ESR 1和AR）和配体下调。此外，虽然VIN不是一种侵袭性疾病，但显著数量的细胞-细胞粘附分子表达的抑制似乎表明向侵袭发展。在回顾细胞凋亡和血管生成时，观察到这些过程在VIN中没有变得显著失调。结论：虽然VIN仍然是一种癌前病变，但它已经显示出癌症的几个特征。(c)2007 Wiley-Liss，Inc.
Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observe that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. (c) 2007 Wiley-Liss, Inc.