Differential regulation of the human gene DAB2IP in normal and malignant prostatic epithelia: cloning and characterization.

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 DAB2IP promoter activity. These data indicate that transcriptional regulation of DAB2IP is responsible for the downregulation of DAB2IP expression in prostate cancer cells.