Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL 33620, USA.
Mol Cancer. 2013 Apr 26;12:32. doi: 10.1186/1476-4598-12-32.
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.
由于获得性耐药和缺乏早期生物标志物，晚期卵巢癌的治疗仍然具有挑战性。在 3q26.2 位点被鉴定为异常表达的基因（即 SnoN/SkiL）与卵巢癌的病理生理学有关。我们之前已经表明，SnoN 在晚期卵巢癌中的表达增加，并改变了细胞对三氧化二砷（As2O3）的反应。
我们现在证明了磷脂移位酶 1（PLSCR1，位于 3q23）的 DNA 拷贝数水平增加（TCGA 数据），其在卵巢细胞系中的转录表达与 SnoN mRNA 高度相关。有趣的是，SnoN 可以在没有/存在干扰素（IFN-2α）的情况下调节 PLSCR1 mRNA 水平。IFN-2α 和 As2O3 处理都可以调节卵巢癌细胞中 PLSCR1 mRNA 水平。然而，SnoN siRNA 不会导致 PLSCR1 蛋白水平改变，暗示需要其他事件来调节其蛋白水平。此外，我们报告 PLSCR1 可以调节 As2O3 细胞反应的某些方面。
我们的发现证明了 PLSCR1 在卵巢癌发展和化疗耐药中的作用值得进一步研究。
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