New targets for therapy in prostate cancer: differential display code 3 (DD3(PCA3)), a highly prostate cancer-specific gene.
Identification of new markers for diagnosis and new targets for therapy would represent a considerable advance in the treatment of prostate cancer. Differential display code 3 (DD3(PCA3)) is a novel gene with characteristics that indicate its potentially valuable role in early identification of malignancy and in the construction of interventions directed specifically toward malignantly transformed cells. DD3(PCA3) has a messenger RNA product that is highly overexpressed in tumors. Compared with other genetic markers that are associated with prostate tissue, DD3(PCA3) is the most specific marker for malignant disease. Indeed, it is not expressed in any other normal human tissue, including breast, bladder, testis, gastrointestinal organ, and musculoskeletal tissue. This specific relation of DD3(PCA3) to prostate tissue has been confirmed by reverse transcription-polymerase chain reaction analysis. Clonal investigation of the DD3(PCA3) transcription unit indicates that the gene has 4 distinct exons, which can give rise to a number of differently sized transcripts. Open reading frame analysis has also confirmed that the DD3(PCA3) exons are populated by an unusual number of stop codons. The dramatic prostate-specific expression and pronounced upregulation of DD3(PCA3) in prostate cancer suggest a unique transcriptional regulation. A quantitative assay for DD3(PCA3) would be a potentially valuable tool for the detection of malignant cells in blood, urine, or other clinical specimens, and it could have important implications for the earlier diagnosis and molecular staging of prostate cancer. Although further studies are needed, gene therapies based on identification to delineate the range of transcription factors that interact with the DD3(PCA3) promoter represent a promising area for preclinical investigation.
Schalken
Jack A
JA
University Medical Center, Nijmegen, Netherlands. J.Schalken@uro.umcn.nl
Hessels
Daphne
D
Verhaegh
Gerald
G
D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008403:Mass Screening; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C479341:prostate cancer antigen 3, human