Abstract
BackgroundAnalysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the “driver” gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21–1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.Methodology/Principal FindingsTo evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.SignificanceCollectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted.
Highlights
Evaluation of the chromosomal region 1q21–1q23, frequently amplified in primary liposarcomas, by fluorescence in situ hybridization and comparative genomic hybridization reduced the list of candidate oncogenes contained by this amplicon to two genes: the activating transcription factor 6 and the dual specificity phosphatase 12 [1]
All the data shown were generated with the use of one individual clone designated F78; we observed similar results in other individual clones as well as in transient expression assays, suggesting that the phenotypes observed are not due to disruption of an unknown gene caused by the insertions of gfp-dusp12 into the genome
This study demonstrates that over-expression of dusp12, may promote cancer development and progression by increasing migration and cell survival
Summary
Evaluation of the chromosomal region 1q21–1q23, frequently amplified in primary liposarcomas, by fluorescence in situ hybridization and comparative genomic hybridization reduced the list of candidate oncogenes contained by this amplicon to two genes: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12) [1]. ATF6 is a transcription factor involved in the unfolded protein response (UPR) which responds to endoplasmic reticulum (ER) stress [2]. In four out of five liposarcomas examined, dusp was expressed significantly higher than atf, suggesting that dusp may be the more relevant target of the 1q21–1q23 chromosomal amplification [1]. Amplification of 1q21–1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp). While atf is an established transcriptional regulator of the unfolded protein response, the potential role of dusp in cancer remains uncharacterized
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
