Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis
Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis
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DOI：
10.1016/j.fertnstert.2004.01.047
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发表时间：
2004-09-01
影响因子：
6.7
通讯作者：
Gregg, JP
中科院分区：
文献类型：
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作者：
Hoffman, PJ;Milliken, DB;Gregg, JP
目的：利用Affymetrix hd - u133a基因芯片（(R)）对正常子宫肌层和子宫平滑肌瘤起源组织进行全局表达谱分析，以鉴定参与肌瘤发育的基因。设计：对平滑肌瘤和正常肌层组织样本的mRNA水平进行全基因组分析。环境：大学研究实验室。患者：8例不同年龄和种族的患者因症状性肌瘤接受手术治疗。干预：从人类病理标本中收集5个肿瘤和5个正常组织后，生成标记的cRNA，并将其杂交到由寡核苷酸组成的阵列中。主要观察指标：子宫肌瘤相对于正常子宫肌层转录物表达水平的量化。结果：基于模型的表达分析显示，在阵列上代表的22,500个转录本中，发现226个基因在平滑肌瘤和正常肌层之间发生大于或等于1.5倍的变化而失调。此外，我们的研究发现了许多失调的凋亡相关基因，特别感兴趣的是TRAIL和Ask1，还发现了许多差异表达的增殖基因，包括TGFB1、PDGFC和两种双特异性磷酸酶。结论：这些基因可能在正常子宫组织平滑肌瘤的发生发展中起重要作用。我们假设，细胞凋亡和增殖过程的失调是肌瘤发展的关键。(C) 2004年，美国生殖医学学会。
Objective: To identify genes involved in fibroid development by performing global expression profiling on tissues of normal myometrium and uterine leiomyoma origin using Affymetrix HG-U133A GeneChip((R)) microarrays.Design: Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples.Setting: University research laboratory.Patient(s): Eight patients of varying age and race undergoing surgery for symptomatic fibroids.Intervention(s): After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays.Main Outcome Measure(s): Quantification of transcript expression levels in uterine fibroids relative to normal myometrium.Result(s): Model-based expression analysis revealed that of the 22,500 transcripts represented on the arrays, 226 genes were found to be dysregulated by a greater than or equal to1.5-fold change between leiomyoma and normal myometrium. Moreover, our research identified many dysregulated apoptosis-related genes, of particular interest was TRAIL and Ask1, and also found numerous differentially expressed proliferation genes, including TGFB1, PDGFC, and two dual specificity phosphatases.Conclusion(s): These results indicate that these genes may play a significant role in the development of leiomyomas from normal uterine tissue. We hypothesize that the deregulation of apoptotic and proliferative processes is pivotal to fibroid development. (C) 2004 by American Society for Reproductive Medicine.