Identification of Sp2 as a transcriptional repressor of carcinoembryonic antigen-related cell adhesion molecule 1 in tumorigenesis
Identification of Sp2 as a transcriptional repressor of carcinoembryonic antigen-related cell adhesion molecule 1 in tumorigenesis
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DOI：
10.1158/0008-5472.can-03-3730
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发表时间：
2004-05-01
期刊：
影响因子：
11.2
通讯作者：
Lin, SH
中科院分区：
文献类型：
--
作者：
Phan, D;Cheng, CJ;Lin, SH
癌胚抗原相关细胞粘附分子1（CEACAM1）肿瘤抑制基因表达下调在前列腺癌、结肠癌和乳腺癌等多种恶性肿瘤中很常见。介导这种下调的机制尚不清楚。在这里，我们报告，下调CEACAM1在前列腺癌细胞中的表达主要发生在转录水平，并介导的Sp2，转录因子的Sp家族的成员。Sp2在体外和体内结合CEACAM1启动子，并且Sp2的瞬时过表达下调正常前列腺上皮细胞中的内源性CEACAM1表达。Sp2似乎通过向CEACAM1启动子募集组蛋白脱乙酰酶活性来抑制CEACAM1基因表达。在人前列腺癌标本中，Sp2表达在前列腺癌细胞中高，但在正常前列腺上皮细胞中低，并且与CEACAM1表达呈负相关。我们的研究表明Sp2的转录抑制是CEACAM1肿瘤抑制基因在前列腺癌中下调的一种机制。
Down-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) tumor suppressor gene expression is common in several malignancies including prostate, colon, and breast cancer. The mechanism that mediates this down-regulation is not known. Here, we report that down-regulation of CEACAM1 expression in prostate cancer cells occurs primarily at the transcriptional level and is mediated by Sp2, a member of the Sp family of transcription factors. Sp2 binds to the CEACAM1 promoter in vitro and in vivo, and transient overexpression of Sp2 down-regulates endogenous CEACAM1 expression in normal prostate epithelial cells. Sp2 appears to repress CEACAM1 gene expression by recruiting histone deacetylase activity to the CEACAM1 promoter. In human prostate cancer specimens, Sp2 expression is high in prostate cancer cells but low in normal prostate epithelial cells and is inversely correlated with CEACAM1 expression. Our studies show that transcriptional repression by Sp2 represents one mechanism by which CEACAM1 tumor suppressor gene is down-regulated in prostate cancer.