Differential regulation of the human gene DAB2IP in normal and malignant prostatic epithelia:: Cloning and characterization
Differential regulation of the human gene DAB2IP in normal and malignant prostatic epithelia:: Cloning and characterization
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DOI：
10.1006/geno.2002.6739
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发表时间：
2002-04-01
期刊：
影响因子：
4.4
通讯作者：
Hsieh, JT
中科院分区：
文献类型：
--
作者：
Chen, H;Pong, RC;Hsieh, JT
人DAB 2 IP（DAB 2 interaction protein）是Ras GTP酶激活蛋白家族的新成员。它与DAB 2直接相互作用，DAB 2抑制许多癌症类型的生长。我们证明了DAB 2 IP在人前列腺癌细胞系中经常下调。预测的DAB 2 IP蛋白（967个氨基酸）与大鼠DIP 1/2蛋白有94.2%的同源性。我们定位了DAB 2 IP的启动子，并研究了其在正常和恶性前列腺癌细胞中的调控。该基因定位于9q33.1-q33.3，跨度约96 kb，具有15个外显子和14个内含子。DAB 2 IP启动子不包含任何典型的TATA盒，这通过具有差异转录起始位点的各种RNA的存在来证明。我们进一步证明，正常前列腺上皮细胞与癌细胞相比具有升高的DAB 2 IP mRNA，这与增加的DAMP启动子活性相关。这些数据表明，转录调控的DAB 2 IP是负责在前列腺癌细胞中的DAB 2 IP表达下调。
Human DAB2IP (for DAB2 interaction protein) is a novel member of the RasGTPase-activating protein family. It interacts directly with DAB2, which suppresses growth of many cancer types. We demonstrated that DAB2IP is often downregulated in human prostate cancer cell lines. The predicted DAB2IP protein (967 amino acids) shares 94.2% homology with the rat DIP1/2 protein. We mapped the promoter of DAB2IP and studied its regulation in normal and malignant prostate cancer cells. This gene is located at 9q33.1-q33.3 and spans approximately 96 kb with 15 exons and 14 introns. The DAB2IP promoter does not contain any typical TATA box-evidenced by the presence of various RNAs with differential transcription starting sites. We further demonstrated that normal prostatic epithelial cells have elevated DAB2IP mRNA compared with cancer cells, which correlates with increased DAMP promoter activity. These data indicate that transcriptional regulation of DAB2IP is responsible for the downregulation of DAB2IP expression in prostate cancer cells.