La Placa Michelangelo, Gibellini Davide, Bianchi Tommaso, Patrizi Annalisa
Department of Clinical and Experimental Medicine, Dermatology Section, University of Bologna, Bologna, Italy.
J Cutan Pathol. 2006 Sep;33(9):608-13. doi: 10.1111/j.1600-0560.2006.00483.x.
Tuberous sclerosis complex (TSC) is associated with mutations in two likely tumor-suppressor genes (TSC1 and TSC2) and characterized by the development of tumor-like growths (angiofibromas) in a variety of tissues and organs, particularly brain and skin.
Employing a DNA-microarray assay, able to detect mRNA production from 1176 different basic genes, we analyzed the gene-expression levels in a cutaneous hamartoma sample from a TSC patient. Altered gene expressions detected by microarray technology were further checked by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in the same material and in cutaneous hamartoma samples obtained from five other TSC patients.
The results obtained by the microarray technology in one hamartoma specimen, confirmed by the RT-PCR results obtained in the same material and in five other hamartoma specimens, demonstrated that TSC-related angiofibromas exhibit significant mRNA overexpression of two genes, represented by MLH-1 and psoriasin.
The overexpression of MLH-1, which codes for a DNA mismatch repair protein, and psoriasin, which codes for a specific chemoattractant factor for CD4+ T cells, implicated in the pathogenesis of inflammatory skin disease, and expressed in excess during abnormal pathways of cell growth, may shed light on the pathogenesis of the proliferative skin lesion.
结节性硬化症（TSC）与两个可能的肿瘤抑制基因（TSC1和TSC2）的突变相关，其特征是在多种组织和器官，特别是脑和皮肤中出现肿瘤样生长（血管纤维瘤）。
我们采用一种能够检测1176个不同基础基因mRNA产生情况的DNA微阵列分析方法，对一名TSC患者的皮肤错构瘤样本中的基因表达水平进行了分析。通过微阵列技术检测到的基因表达改变，在同一材料以及从其他五名TSC患者获取的皮肤错构瘤样本中，进一步通过定量逆转录聚合酶链反应（RT-PCR）进行了验证。
微阵列技术在一个错构瘤标本中获得的结果，经同一材料以及其他五个错构瘤标本的RT-PCR结果证实，表明TSC相关的血管纤维瘤呈现出两个基因（以MLH-1和银屑素为代表）的显著mRNA过表达。
编码DNA错配修复蛋白的MLH-1以及编码CD4+ T细胞特异性趋化因子（参与炎症性皮肤病发病机制且在细胞生长异常途径中过度表达）的银屑素的过表达，可能为增生性皮肤病变的发病机制提供线索。
