Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns
Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns
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DOI：
10.1073/pnas.93.9.4120
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发表时间：
1996-04-30
影响因子：
11.1
通讯作者：
Minna, JD
中科院分区：
文献类型：
--
作者：
Sekido, Y;Bader, S;Minna, JD
脑信号蛋白-酸性脑信号蛋白是一个保守的编码神经生长锥导向信号的基因家族。我们已经在染色体区域3p21.3中鉴定了人脑信号蛋白家族的另外两个成员[人脑信号蛋白A（V）和人脑信号蛋白IV]，其中几个小细胞肺癌（SCLC）细胞系表现出指示肿瘤抑制基因的纯合缺失。人脑信号蛋白A（V）与鼠脑信号蛋白A具有86%的氨基酸同源性，而脑信号蛋白IV与鼠脑信号蛋白E最密切相关，具有50%的同源性。这些脑信号蛋白基因在两个GTP结合蛋白基因GNAI-2和GNAT-1两侧相距约70 kb。相反，其他人脑信号蛋白基因序列（人脑信号蛋白LII和鼠脑信号蛋白B和C的同源物）不位于3号染色体上。人脑信号蛋白A（V）在体外被翻译成一种90 kDa的蛋白质，在内质网中积累。人类脑信号蛋白A（V）（3.4-kb mRNA）和IV（3.9-和2.9-kb mRNA）基因在多种人类神经和非神经组织中大量表达，但存在差异。人脑信号蛋白A（V）仅在23个SCLC中的1个和16个非SCLC中的7个中表达，而脑信号蛋白IV在23个SCLC中的19个和16个非SCLC中的13个中表达。对semaphorin A（V）的突变分析显示，40例肺癌中有3例发生了突变（1例为种系突变）。我们的数据表明，需要确定人类semaphorins A（V）和IV在非神经组织中的功能及其在肺癌发病机制中的作用。
Semaphorins acid collapsins make up a family of conserved genes that encode nerve growth cone guidance signals. We have identified two additional members of the human semaphorin family [human semaphorin A(V) and human semaphorin IV] in chromosome region 3p21.3, where several small cell lung cancer (SCLC) cell lines exhibit homozygous deletions indicative of a tumor suppressor gene. Human semaphorin A(V) has 86% amino acid homology with murine semaphorin A, whereas semaphorin IV is most closely related to murine semaphorin E, with 50% homology. These semaphorin genes are approximate to 70 kb apart flanking two GTP-binding protein genes, GNAI-2 and GNAT-1. In contrast, other human semaphorin gene sequences (human semaphorin LII and homologues of murine semaphorins B and C) are not located on chromosome 3. Human semaphorin A(V) is translated in vitro into a 90-kDa protein, which accumulates at the endoplasmic reticulum. The human semaphorin A(V) (3.4-kb mRNA) and IV (3.9- and 2.9-kb mRNAs) genes are expressed abundantly but differentially in a variety of human neural and nonneural tissues. Human semaphorin A(V) was expressed in only 1 out of 23 SCLCs and 7 out of 16 non-SCLCs, whereas semaphorin IV was expressed in 19 out of 23 SCLCs and 13 out of 16 non-SCLCs. Mutational analysis in semaphorin A(V) revealed mutations (germ line in one case) in 3 of 40 lung cancers. Our data suggest the need to determine the function of human semaphorins A(V) and IV in nonneural tissues and their role in the pathogenesis of lung cancer.