Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells
1 Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL 33620, USA
2 Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, USA
3 University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA
Molecular Cancer 2013, 12:32 doi:10.1186/1476-4598-12-32Published: 26 April 2013
Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).
We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.
Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.