The Galanin Signaling Cascade is a Candidate Pathway Regulating Oncogenesis in Human Squamous Cell Carcinoma
The Galanin Signaling Cascade is a Candidate Pathway Regulating Oncogenesis in Human Squamous Cell Carcinoma
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DOI：
10.1002/gcc.20626
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Hata, Akira
中科院分区：
文献类型：
--
作者：
Sugimoto, Takashi;Seki, Naohiko;Hata, Akira
为了确定鳞状细胞癌（SCC）的推定生物标志物，使用阵列比较基因组杂交（CGH）和oligo微阵列技术对10个鳞状细胞癌细胞系进行了平行染色体改变和基因表达研究。SCC中最常见的变化是Iq13.1-13.3的增加和18q12.1-23的减少。此外，使用微阵列分析测量了SCC中这两个位点的一组基因的表达水平。将阵列- cgh与微阵列数据相结合，鉴定出10个11q13.1-13.3基因和6个18q12.1-23基因表达与染色体改变相关。为了验证鉴定基因的表达水平，我们使用了来自早期临床标本研究的表达分析数据。在临床样本中，11q13.1-13.3位点的6个基因（GAL、GSTP1、MRPL11、MRPL21、SF382、YIF1A）和18q23位点的1个基因（GALR1）在正常和肿瘤样本中表现出显著差异。编码神经肽甘丙氨酸的GAL和甘丙氨酸受体GALR1被确定为SCC肿瘤发生的候选基因。real-time PCR检测GAL、GALR1、GALR2、GALR3的表达水平。GAL与GALR1的表达率呈显著负相关。GALR1是一种g蛋白偶联受体，可激活gtp结合蛋白触发信号级联反应，如丝裂原活化蛋白激酶途径，是一种完善的有丝分裂途径。这进一步支持了参与GAL信号级联的基因是SCC中肿瘤发生调节的候选基因的假设。(c) 2008 Wiley-Liss, Inc。
To identify putative biomarkers in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-comparative genomic hybridization (CGH) and oligo-microarray techniques. The most frequent changes were gains of I Iq13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. To verify the expression levels of the identified genes, we used expression analysis data derived from our earlier study of clinical specimens. In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF382, and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a significant difference between normal and tumor samples. GAL, coding for the neuropeptide galanin, and GALR1, a galanin receptor, were identified as candidate genes of oncogenesis in SCC. The expression levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time PCR. The expression ratio between GAL and GALR1 showed a significant negative correlation. GALR1 is a G-protein-coupled receptor that activates GTP-binding proteins to trigger signaling cascades such as the mitogen-activated protein kinase pathway, and is a well-established mitogenic pathway. This further supports the hypothesis that the genes involved in the GAL signaling cascade are candidates for regulation of oncogenesis in SCC. (c) 2008 Wiley-Liss, Inc.