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A new treatment approach for Malignant Melanoma basing on analysis of expression pattern of homeobox genes

基于同源框基因表达模式分析的恶性黑色素瘤新治疗方法

基本信息

批准号：
16390505
负责人：
YAMAMOTO Yuhei
金额：
$ 4.99万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390505/
关键词：
Malignant Melanoma HOX gene Metastasis Nevus Pigmentosus

项目摘要

HOX genes act as master genes to control morphogenesis. In human, HOX genes form 4 clusters composing 9 to 11 HOX genes (39 genes in total) on different chromosomes. We hypothesized that aberrant expression of HOX genes was associated with development and subsequent progression of melanoma and that the 39 HOX gene expression pattern determined the sites where melanoma grew. The expression levels of 39 HOX genes in 15 human cutaneous melanoma specimens and 7 nevus pigmentosus specimens were quantified by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA11,A13,B9,D12 and D13 in melanoma were higher than those in nevus pigmentosus and that the expression levels of HOXA11, B2 and C13 were significantly different between pT4 melanoma and pT1 to pT3 melanoma. It was most notable that the expression levels of HOXA1,A2,C4 and B13 in melanoma with distant metastasis were higher than those in melanoma without it. On the other hand, we found no relationship between HOX genes expression patterns and the growing sites of melanoma. These results indicated that the misexpressions of some specific HOX genes were implicated in melanoma genesis and metastasis but had no linkage with melanoma sites.And we did similar experiment of PAX genes which are also Homeobox genes.

HOX基因是控制形态发生的主控基因。在人类中，HOX基因在不同的染色体上形成4个簇，由9 ~ 11个HOX基因组成，共39个基因。我们假设HOX基因的异常表达与黑色素瘤的发展和随后的进展有关，并且39个HOX基因的表达模式决定了黑色素瘤生长的部位。采用基于实时RT-PCR方法的综合分析系统，对15例人类皮肤黑色素瘤标本和7例色素痣标本中39个HOX基因的表达水平进行定量分析。我们发现HOXA11、A13、B9、D12和D13在黑色素瘤中的表达水平高于色素痣，并且HOXA11、B2和C13在pT4黑色素瘤和pT1至pT3黑色素瘤中的表达水平有显著差异。最值得注意的是，有远处转移的黑色素瘤中HOXA1、A2、C4和B13的表达水平高于无远处转移的黑色素瘤。另一方面，我们没有发现HOX基因表达模式和黑色素瘤生长部位之间的关系。这些结果表明，一些特定的HOX基因的错误表达与黑色素瘤的发生和转移有关，但与黑色素瘤的部位没有关联。我们对PAX基因做了类似的实验它也是同源盒型基因。