%0 Journal Article
%T Expression of Tra2¦Â in Cancer Cells as a Potential Contributory Factor to Neoplasia and Metastasis
%A Andrew Best
%A Caroline Dagliesh
%A Ingrid Ehrmann
%A Mahsa Kheirollahi-Kouhestani
%A Alison Tyson-Capper
%A David J. Elliott
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/843781
%X The splicing regulator proteins SRSF1 (also known as ASF/SF2) and SRSF3 (also known as SRP20) belong to the SR family of proteins and can be upregulated in cancer. The SRSF1 gene itself is amplified in some cancer cells, and cancer-associated changes in the expression of MYC also increase SRSF1 gene expression. Increased concentrations of SRSF1 protein promote prooncogenic splicing patterns of a number of key regulators of cell growth. Here, we review the evidence that upregulation of the SR-related Tra2¦Â protein might have a similar role in cancer cells. The TRA2B gene encoding Tra2¦Â is amplified in particular tumours including those of the lung, ovary, cervix, stomach, head, and neck. Both TRA2B RNA and Tra2¦Â protein levels are upregulated in breast, cervical, ovarian, and colon cancer, and Tra2¦Â expression is associated with cancer cell survival. The TRA2B gene is a transcriptional target of the protooncogene ETS-1 which might cause higher levels of expression in some cancer cells which express this transcription factor. Known Tra2¦Â splicing targets have important roles in cancer cells, where they affect metastasis, proliferation, and cell survival. Tra2¦Â protein is also known to interact directly with the RBMY protein which is implicated in liver cancer. 1. Introduction Cancer is associated with a number of distinctive disease hallmarks [1]. These hallmarks include the ability of cancer cells to continuously divide by maintaining proliferative signalling pathways and to evade growth suppressors, to resist cell death; to induce angiogenesis to ensure a supply of oxygen and nutrition, and to invade other parts of the body (metastasis). These hallmarks of cancer cells occur against other changes including decreasing genome stability and inflammation [1]. Changes in splicing patterns in cancer cells compared to normal cells can contribute to each of these cancer hallmarks through effects on the expression patterns of important protein isoforms which regulate cell behaviour [2¨C4]. The splicing alterations which occur in cancer cells are partially due to changes in the activity and expression of core spliceosome components [5] and in the RNA binding proteins which regulate alternative exon inclusion [6]. Changes in the splicing environment in cancer cells might have therapeutic implications. Drugs which target the spliceosome are also being developed as potential therapies for treating cancer patients [7]. In this review, we particularly examine the potential role of the splicing regulator Tra2¦Â as a modulator of gene function in cancer cells. Tra2¦Â is
%U http://www.hindawi.com/journals/ijcb/2013/843781/