ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells
ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells
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DOI：
10.1002/pros.20633
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发表时间：
2007-09-15
期刊：
影响因子：
2.8
通讯作者：
Chaudhary, Jaideep
中科院分区：
文献类型：
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作者：
Asirvatharn, Ananthi J.;Carey, Jason P. W.;Chaudhary, Jaideep
背景资料。分化抑制蛋白(ID)在前列腺癌(PCa)中有表达。方法利用基因特异性小干扰RNA(SiRNA)沉默前列腺癌细胞系LNCaP、DU145和PC3中的Id1、Id2或Id3。采用实时荧光定量聚合酶链式反应(Real-Time-PCR)技术，研究ID基因沉默对细胞凋亡(p53、SNAIL2)、增殖(p21、p16)、肿瘤侵袭相关基因(E-cadherin、MMP9)表达的影响。结果在缺乏E蛋白的情况下，ID蛋白调控CDKNIs p16和p21的表达。在E蛋白阴性或阳性的PCa细胞系中，Id1和ID3的缺失分别上调或下调了E-钙粘附素的表达。在p16和p21缺失的PC3细胞中，ID基因对细胞增殖的影响也不依赖于CDKNIs。Id2的P53非依赖性抗细胞凋亡作用部分是通过转录抑制因子SNAI2介导的。MMP9似乎是所有三种ID基因(Id1、Id2和Id3)的共同靶点。结论：ID蛋白对细胞增殖和凋亡的整体作用不依赖于E蛋白。然而，E蛋白可以决定反应的大小，甚至在某些情况下逆转ID介导的靶基因表达。联合评估E蛋白和ID蛋白的表达将有助于更好地了解ID蛋白的分子作用机制，并增加其在PCa中的预后意义。
BACKGROUND. The inhibitor of differentiation (Id) proteins are expressed in prostate cancer (PCA). However, there is a general lack of Id isoform-specific downstream effectors.METHODS. Id1, Id2, or Id3 were silenced in PCA cell lines LNCaP, DU145, and PC3 using gene-specific small interfering RNA (siRNA). The effect of Id gene silencing on representative genes involved in apoptosis (p53, SNAIL2), proliferation (p21, p16), and tumor invasion (E-cadherin and MMP9) was investigated by real-time PCR. Expression of E-proteins, the primary Id interaction partners was also evaluated to understand the molecular mechanism of action.RESULTS. The Id proteins regulated the expression of CDKNIs p16 and p21 even in the absence of E-proteins. Loss of Id1 and Id3 up- or downregulated E-cadherin expression in E-protein negative or positive PCA cell lines, respectively. The effect of Id genes on cell proliferation was also independent of CDKNIs in p16 and p21 null PC3 cells. The p53-independent anti-apoptotic effect of Id2 was mediated in part by transcriptional repressor SNAI2. MMP9 seems to be the common target of all three Id genes (Id1, Id2, and Id3).CONCLUSIONS. The overall effect of Id proteins on proliferation and apoptosis is independent of E-proteins. E-proteins can however determine the magnitude of response or in some cases even reverse the Id-mediated target gene expression. Evaluating E-protein expression in conjunction with Id proteins will allow better understanding of the molecular mechanism of action of Id proteins and increase their prognostic significance in PCA.