Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors
Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors
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DOI：
10.1007/s00401-006-0032-5
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发表时间：
2006-03-01
影响因子：
12.7
通讯作者：
Henriksson, R
中科院分区：
文献类型：
--
作者：
Guo, DS;Nilsson, J;Henriksson, R
我们之前已经描述了三个人类富含亮氨酸的重复序列和免疫球蛋白样结构域（LRIG）基因和蛋白，命名为LRIG1-3，并提出它们可能作为肿瘤生长的抑制因子。LRIG1跨膜蛋白可拮抗表皮生长因子受体家族酪氨酸激酶的活性。本研究通过免疫组化方法，对404例星形胶质细胞肿瘤中LRIG1-3在人胶质瘤细胞系和对照匹配胶质瘤组织中的mRNA表达水平进行了检测，表征了LRIG3-GFP融合蛋白的亚细胞定位，并分析了LRIG1-3亚细胞定位与临床参数的关系。LRIG1-3 mRNA在所有人类胶质瘤细胞系和匹配的胶质瘤样本中均检测到，且表达水平差异较大。异位表达的LRIG3-GFP定位于核周和细胞质室，以及转染的胶质瘤细胞的细胞表面。LRIG1-3的核周染色与低WHO分级和更好的患者生存率相关。LRIG3的核周染色与较低的增殖指数相关，并且除了肿瘤分级之外，这是一个独立的预后因素。此外，在III级和IV级肿瘤组中，核周LRIG3染色与更好的生存率显著相关。这些结果提示LRIG1-3的表达和亚细胞定位可能在星形细胞肿瘤的发病和预后中起重要作用。
We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3-GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3-GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.