Liu Xiao-Qiong, Sun Min, Chen Han-Kui, Li Jing-Xiang, Pan Zhi-Gang, Long Qing-Xin, Wang Xun-Zhang, Zeng Yi-Xin
Department of Pathology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China.
Ai Zheng. 2003 Jan;22(1):16-20.
BACKGROUND & OBJECTIVE: Though the molecular etiology of nasopharyngeal carcinoma(NPC) is currently unknown, evidence from both loss of heterozygosity analysis and functional studies suggested that there are NPC-associated tumor suppressor genes(TSGs) residing in chromosome 3p21.3. Recently, two members of semaphorin family, SEMA3B and SEMA3F gene, located at 3p21.3, were characterized as TSGs. Studies showed that SEMA3B and SEMA3F are capable of suppressing the growth of tumor cells and inducing apoptosis. Loss of SEMA3B mRNA expression or aberrant SEMA3F cellular localization were found in lung cancers. In order to investigate the involvement of SEMA3B and SEMA3F in NPC, the authors examined both mutation and expression of these two genes in NPC.
The entire coding regions, the splice donor/acceptor sites, and partial regulatory regions of SEMA3B and SEMA3F gene were screened for mutations by PCR-sequencing in 21 primary NPC tumors and 2 NPC cell lines(CNE2 and SUNE1). The mRNA expression levels were determined by semi-quantitative RT-PCR analysis.
No somatic mutation was found in either SEMA3B or SEMA3F gene. However, two missense polymorphisms including Thr415Ile and lle242Met were found in SEMA3B in NPC. For the Thr415Ile polymorphism, the Ile allele type which leads to SEMA3B function defects was predominant in NPC with the allele frequency of 64% (27/42). SEMA3B mRNA was expressed in all 6 non-neoplastic nasopharyngeal epithelia, but was absent or down-regulated in 76% (16/21) of primary NPC tumors. No significant difference of SEMA3B expression was observed between NPC and noncancerous controls.
High frequency of SEMA3B expression alterations suggests that the inactivation of this gene was strongly associated with NPC. SEMA3B may be a tumor suppressor on 3p21.3 involved in NPC.
尽管鼻咽癌（NPC）的分子病因目前尚不清楚，但杂合性缺失分析和功能研究的证据均表明，位于3p21.3的基因存在与NPC相关的肿瘤抑制基因（TSG）。最近，位于3p21.3的信号素家族的两个成员，即SEMA3B和SEMA3F基因，被鉴定为TSG。研究表明，SEMA3B和SEMA3F能够抑制肿瘤细胞的生长并诱导凋亡。在肺癌中发现SEMA3B mRNA表达缺失或SEMA3F细胞定位异常。为了研究SEMA3B和SEMA3F在NPC中的作用，作者检测了这两个基因在NPC中的突变和表达情况。
通过PCR测序，在21例原发性NPC肿瘤和2株NPC细胞系（CNE2和SUNE1）中筛查SEMA3B和SEMA3F基因的整个编码区、剪接供体/受体位点及部分调控区的突变情况。采用半定量RT-PCR分析测定mRNA表达水平。
在SEMA3B和SEMA3F基因中均未发现体细胞突变。然而，在NPC的SEMA3B中发现了两个错义多态性，包括Thr415Ile和Ile242Met。对于Thr415Ile多态性，导致SEMA3B功能缺陷的Ile等位基因类型在NPC中占主导地位，等位基因频率为64%（27/42）。SEMA3B mRNA在所有6例非肿瘤性鼻咽上皮中均有表达，但在76%（16/21）的原发性NPC肿瘤中缺失或下调。NPC与非癌对照之间SEMA3B表达无显著差异。
SEMA3B表达改变的高频率表明该基因的失活与NPC密切相关。SEMA3B可能是3p21.3上参与NPC的肿瘤抑制基因。
