title: Intronic promoters and their noncoding transcripts: a new source of cancer-associated genes.
abstract: Recent studies of mammalian genomes suggest that alternative promoters are associated with various disorders, including cancer. Here we present an intronic promoter of the murine proteinase 3 gene, which drives the expression of an alternative mRNA in intron 2 of the prtn3 gene. The proximal promoter sequences were identified and a series of promoter deletion constructs were used to identify the sequence elements that are required for basal promoter activity. Expression of the homeobox transcription factor CUX1 p75 isoform was found to suppress the activity of the alternative PR3 promoter. Data base analyses, multiple alignments and expression data showed that the intronic PR3 promoter is active in leukemia and other tumor cells as well as in mouse embryo, male mammary gland and bone marrow. In the spleen, the transcript is exclusively expressed by Gr-1(int) /CD11b(+) cells, which are also known as myeloid-derived suppressor cells (MDSCs). In humans, an alternative transcript of the PR3-gene could be detected in the bone marrow and in various cancer cell lines but not in primary leukemia cells, suggesting a species-overarching function of this kind of promoter. Therefore, the alternative PR3 promoter and its mRNA may be useful tools to investigate the fate of hematopoietic stem cells.
authors.affiliation: I. Department of Medicine, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Relle
authors.forename: Marc
authors.initials: M
authors.lastname: Becker
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwarting
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D005801:Genes, Homeobox / Q000235:genetics; D018922:HL-60 Cells; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007438:Introns; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053146:Myeloblastin / Q000235:genetics; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D022661:RNA, Untranslated; D014157:Transcription Factors; D053146:Myeloblastin