hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33.
hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33.
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DOI：
10.1007/s11060-010-0314-6
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发表时间：
2011-04
影响因子：
3.9
通讯作者：
Basile, Lena A.
中科院分区：
文献类型：
--
作者：
Junes-Gill, Katiana S.;Gallaher, Timothy K.;Gluzman-Poltorak, Zoya;Miller, Joseph D.;Wheeler, Christopher J.;Fan, Xuemo;Basile, Lena A.
人类基因组计划的完成导致了许多未知的新基因的发现。这一壮举为基于新的生物学功能和途径治疗人类疾病的新疗法的未来发展铺平了道路。为此，我们对来自纯化的造血干细胞群体的内部微阵列数据进行了生物信息学分析。这一努力导致了HSS1(含造血信号肽的分泌型1)及其剪接变异体HSM1(含造血信号肽的膜结构域1)的发现。HSS1基因在进化上在物种、门甚至包括哺乳动物、无脊椎动物和植物在内的王国中都是保守的。结构分析表明，HSS1与已知蛋白质或已知蛋白质结构域没有同源性，表明它是一个真正的新蛋白质。有趣的是，人类HSS1(HHSS1)基因位于染色体19q13.33，这是一个与多种癌症有关的基因组区域，包括恶性胶质瘤。HHSS1在人脑胶质瘤来源的A172和U87细胞系中稳定表达，与模型细胞相比，它们的增殖率大大降低。体内外hHSS1的表达均显著影响U87细胞的恶性表型。此外，初步免疫组织化学分析显示，在四个高级别星形细胞瘤中有两个(多形性胶质母细胞瘤，WHO IV)的hHSS1/HSM1免疫反应增强，而在所有四个低级别弥漫性星形细胞瘤(WHO II级)中hHSS1/HSM1的表达都很低。基因芯片数据进一步支持hHSS1在高级别胶质瘤中的高表达，这表明间叶细胞亚类胶质瘤唯一上调hHSS1。我们的数据显示，HSS1是一种真正新的蛋白质，定义了一类新的分泌因子，它可能在癌症，特别是胶质瘤中发挥重要作用。
The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-house microarray data derived from purified hematopoietic stem cell populations. This effort led to the discovery of HSS1 (Hematopoietic Signal peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily conserved across species, phyla and even kingdoms, including mammals, invertebrates and plants. Structural analysis showed no homology between HSS1 and known proteins or known protein domains, indicating that it was a truly novel protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome 19q13.33, a genomic region implicated in various cancers, including malignant glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines greatly reduced their proliferation rates compared to mock-transfected cells. hHSS1 expression significantly affected the malignant phenotype of U87 cells both in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1 in high-grade gliomas was further supported by microarray data, which indicated that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal that HSS1 is a truly novel protein defining a new class of secreted factors, and that it may have an important role in cancer, particularly glioma.
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影响因子：
11.2
作者：
Lee YJ;Koch M;Karl D;Torres-Collado AX;Fernando NT;Rothrock C;Kuruppu D;Ryeom S;Iruela-Arispe ML;Yoon SS
通讯作者：
Yoon SS
影响因子：
4.4
作者：
Smith, JS;Tachibana, I;Jenkins, RB
通讯作者：
Jenkins, RB
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
影响因子：
6.2
作者：
Yang, P;Kollmeyer, TM;Jenkins, RB
通讯作者：
Jenkins, RB
影响因子：
7.3
作者：
Cheng H;Liu P;Wang ZC;Zou L;Santiago S;Garbitt V;Gjoerup OV;Iglehart JD;Miron A;Richardson AL;Hahn WC;Zhao JJ
通讯作者：
Zhao JJ