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Molecular Biology and Genetics |
Urology Research Laboratory, University Hospital Nijmegen, 6500 HB Nijmegen, the Netherlands [M. J. G. B., A. v. B., G. W. V., F. P. S., J. A. S., F. M. J. D.]; Department of Urology, Canisius Wilhelmina Hospital, 6500 GS Nijmegen, the Netherlands [H. F. M. K.]; and James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-2101 [N. R., W. B. I.]
Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the Western male population. Despite the tremendous efforts that have been made to improve the early detection of this disease and to design new treatment modalities, there is still an urgent need for new markers and therapeutic targets for the management of prostate cancer patients. Using differential display analysis to compare the mRNA expression patterns of normal versus tumor tissue of the human prostate, we identified a cDNA, DD3, which is highly overexpressed in 53 of 56 prostatic tumors in comparison to nonneoplastic prostatic tissue of the same patients. Reverse transcription-PCR analysis using DD3-specific primers indicated that the expression of DD3 is very prostate specific because no product could be amplified in 18 different normal human tissues studied. Also, in a sampling of other tumor types and a large number of cell lines, no expression of DD3 could be detected. Molecular characterization of the DD3 transcription unit revealed that alternative splicing and alternative polyadenylation occur. The fact that no extensive open reading frame could be found suggests that DD3 may function as a noncoding RNA. The DD3gene was mapped to chromosome 9q21–22, and no homology of DD3 to any gene present in the computer databases was found. Our data indicate that DD3is one of the most prostate cancer-specific genes yet described, and this makes DD3 a promising marker for the early diagnosis of prostate cancer and provides a powerful tool for the development of new treatment strategies for prostate cancer patients.
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