CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability
CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability
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DOI：
10.1158/0008-5472.can-05-0650
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发表时间：
2005-07-15
期刊：
影响因子：
11.2
通讯作者：
Watson, DK
中科院分区：
文献类型：
--
作者：
Fraser, MM;Watson, PM;Watson, DK
CASM(癌症相关的类Sm)最初是基于胰腺癌和几种癌症来源的细胞系中表达增加而被识别的。CASM编码一个133个氨基酸的蛋白质，包含两个Sm基序，在常见的小核RNA蛋白和LSM(Like-Sm)蛋白家族中发现。与正常前列腺组织和原代前列腺上皮细胞相比，部分原发前列腺癌和前列腺癌来源的细胞系CASM表达升高。在DU145细胞中表达反义CASM RNA导致CASM蛋白水平降低和转化表型减少，通过体外锚定非依赖性生长和体内严重联合免疫缺陷小鼠的肿瘤形成来衡量。更多的数据表明，腺病毒转导反义CASM通过改变细胞周期进程来抑制前列腺癌细胞系的生长，并与细胞周期蛋白B1和CDK1蛋白的表达减少有关。与反义处理的细胞未能进入有丝分裂一致，微阵列分析发现NEK2和核磷蛋白/B23的表达发生了变化。虽然CASM促进肿瘤转化和细胞增殖的机制尚不清楚，但已表明CASM的酵母同源物(spb8/LSm1)是特定mRNA5‘到3’降解所必需的。我们提供的数据与CASM在人类细胞中的类似作用一致，支持这样的假设，即在癌症中观察到的CASM表达增加会导致多个基因转录本的不稳定，从而导致癌细胞的突变子表型。
CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm encodes a 133 amino acid protein that contains two Sm motifs found in the common small nuclear RNA proteins and the LSm (like-Sm) family of proteins. Compared with normal human prostate tissue and primary prostate epithelial cells, some primary prostate tumors and prostate cancer-derived cell lines have elevated CaSm expression. Expression of antisense CaSm RNA in DU145 cells results in reduced CaSm protein levels and less transformed phenotype, measured by anchorage-independent growth in vitro and tumor formation in severe combined immunodeficient mice in vivo. Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins. Consistent with failure of antisense-treated cells to enter mitosis, microarray analysis identified altered expression of NEK2 and nucleophosmin/B23. Although the mechanisms by which CaSm contributes to neoplastic transformation and cellular proliferation are unknown, it has been shown that the yeast homologue (spb8/LSm1) of CaSm is required for 5' to 3' degradation of specific mRNAs. We provide data consistent with a similar role for CaSm in human cells, supporting the hypothesis that elevated CaSm expression observed in cancer leads to destabilization of multiple gene transcripts, contributing to the mutator phenotype of cancer cells.