Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancers
Down-regulation of members of glycolipid-enriched membrane raft gene family, MAL and BENE, in cervical squamous cell cancers
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DOI：
10.1111/j.1341-8076.2004.00156.x
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发表时间：
2004-02-01
影响因子：
1.6
通讯作者：
Emi, M
中科院分区：
文献类型：
--
作者：
Hatta, M;Nagai, H;Emi, M
持续性人乳头瘤病毒感染导致受感染的上皮细胞失去细胞极性，导致细胞转化。富含糖脂的膜筏参与上皮细胞顶端膜蛋白的极化分选，甚至参与信号转导。MAL和贝内是GEM筏用于膜蛋白顶端分选的机器的重要组成部分。在这项研究中，我们证明了与相应的非癌子宫鳞状细胞相比，超过三分之二的原发性子宫颈鳞状细胞癌中MAL和贝内mRNA的下调（MAL和贝内分别为20例中的14例和15例）。在MAL和贝内基因组区域的微卫星等位基因分析和基于HpaII-PCR的甲基化分析中，等位基因丢失或超甲基化并不伴随MAL或贝内mRNA在人类原发性宫颈癌中的表达下调。此外，我们注意到这些基因在已建立的宫颈癌细胞系中下调。这些结果表明，MAL和贝内基因的下调，这是细胞极化分选系统的重要组成部分，在人类宫颈鳞状细胞癌的发展中发挥重要作用。
Persistent human papillomavirus infections cause infected epithelial cells to lose cellular polarity leading to cell transformation. Glycolipid-enriched membrane (GEM) rafts are implicated in polarized sorting of apical membrane proteins in epithelial cells and even in signal transduction. The MAL and BENE are essential component of the GEM raft's machinery for apical sorting of membrane proteins. In this study we demonstrated down-regulation of MAL and BENE mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of 20 cases, for MAL and BENE, respectively) when compared to corresponding non-cancerous uterine squamous cells. Allelic loss or hyper-methylation was not accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of the MAL and BENE genomic region. In addition, we note down-regulation of these genes in established cervical cancer cell lines. These results suggest that down-regulation of MAL and BENE genes, which are essential components of the cellular polarized sorting system, play an important role in human cervical squamous cell cancer development.