Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers
Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers
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DOI：
10.1111/apm.12030
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发表时间：
2013-07-01
期刊：
影响因子：
2.8
通讯作者：
Lee, Sug H.
中科院分区：
文献类型：
--
作者：
Kim, Min S.;Je, Eun M.;Lee, Sug H.
越来越多的证据表明，泛素化过程的改变参与了癌症的发病机制。Speckle-type POZ蛋白（SPOP）是Cul 3泛素化过程中的一个重要衔接子。近年来研究发现，SPOP可能是一种抑癌基因（TSG），在前列腺癌（PCA）中发现了SPOP的体细胞突变。本研究旨在探讨SPOP蛋白表达的改变和SPOP基因的体细胞突变是否是肿瘤的特征。本研究应用单链构象多态性（SSCP）技术对45例胃癌、45例结直肠癌和45例前列腺癌组织中SPOP基因体细胞突变进行了分析。应用免疫组化方法检测60例胃癌、60例结直肠癌和60例前列腺癌中SPOP蛋白的表达。在SPOP基因编码序列中检测到3个体细胞错义突变（p.Ser14Leu、p.Tyr87Cys和p.Phe133Leu）。在2例PCA和1例CRC中观察到突变。值得注意的是，p.Phe133Leu是早期研究中报告的复发性突变。SPOP蛋白在正常胃、结肠和前列腺上皮细胞中均有表达，而在胃癌、结直肠癌和前列腺癌中的表达分别为30%、20%和37%。我们的数据表明SPOP表达缺失在GC、CRC和PCA中是常见的，但是本研究中SPOP的体细胞突变在这些肿瘤中是罕见的。此外，这些数据提供了一种可能性，即SPOP基因表达的缺失可能通过改变SPOP的TSG功能在癌症发病机制中发挥作用。
Mounting evidence exists that alterations of ubiquitination processes are involved in cancer pathogenesis. Speckle-type POZ protein (SPOP) is a key adaptor for Cul3-based ubiquitination process. Recent studies reported that SPOP may be a tumor suppressor gene (TSG) and somatic mutation of SPOP was detected in prostate cancer (PCA). The aim of this study was to see whether alterations of SPOP protein expression and somatic mutation of SPOP gene are features of cancers. In this study, we analyzed SPOP somatic mutation in 45 gastric (GC), 45 colorectal cancer (CRC) and 45 PCA by single-strand conformation polymorphism (SSCP). Also, we analyzed SPOP protein expression in 60 GC, 60 CRC and 60 PCA by immunohistochemistry. Overall, we detected three somatic missense mutations of SPOP gene in the coding sequences (p.Ser14Leu, p.Tyr87Cys and p.Phe133Leu). The mutations were observed in two PCA and one CRC. Of note, the p.Phe133Leu was a recurrent mutation reported in an earlier study. In the immunohistochemistry, SPOP protein was expressed in normal gastric, colonic and prostate epithelial cells, whereas it was lost in 30% of GC, 20% of CRC and 37% of PCA. Our data indicate that loss of SPOP expression was common in GC, CRC and PCA, but somatic mutation of SPOP in this study was rare in these tumors. Also, the data provide a possibility that loss of expression of SPOP gene might play a role in cancer pathogenesis by altering TSG functions of SPOP.