Back to Search
Start Over
DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes
- Source :
- Oncogene. 28:2142-2151
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Cytogenetic analysis has identified 12p gain as the most frequent abnormality in human testicular germ cell tumors (TGCTs). It has been suggested that amplification and overexpression of stem cell-associated genes, including cyclin-D2, on the human chromosome 12p region are involved in germ cell tumorigenesis. By subtractive cDNA analysis, we identified Ddx1, a member of the DEAD-box protein family, as a gene predominantly expressed in the primordial germ cells of mouse embryos. Knockdown of Ddx1 in a mouse spermatogonia-derived cell line, GC-1spg, by short interference RNA repressed the expression of cyclin-D2, CD9 and GDF3 genes. In the mouse cyclin-D2 gene, a genomic DNA region between -348 and -329 was responsible for transcriptional activation by DDX1 based on reporter and gel shift assays. Similarly, DDX1 knockdown in the human TGCT cell line NEC8 repressed the expression of stem cell-associated genes localized on chromosome 12p13.3, including cyclin-D2, CD9 and NANOG. DDX1-knocked-down TGCT cells could not form solid tumors in nude mice. Furthermore, in situ hybridization revealed that DDX1 mRNA was produced in both seminoma and nonseminoma types of human TGCT samples. We conclude that DDX1 is a critical factor for testicular tumorigenesis.
- Subjects :
- Male
Transcriptional Activation
Homeobox protein NANOG
Cancer Research
Molecular Sequence Data
Biology
medicine.disease_cause
DEAD-box RNA Helicases
Mice
Testicular Neoplasms
Cell Line, Tumor
Cyclins
Gene expression
Genetics
medicine
Animals
Cyclin D2
Humans
RNA, Messenger
RNA, Small Interfering
Molecular Biology
Gene
Regulation of gene expression
Gene knockdown
Chromosomes, Human, Pair 12
Base Sequence
Stem Cells
Spermatozoa
Molecular biology
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Cell Transformation, Neoplastic
medicine.anatomical_structure
Stem cell
Carcinogenesis
Germ cell
Protein Binding
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....82d68b83d1d274a043f2bf44c12188e2