Poster Presentation 25th Lorne Cancer Conference 2013

Dynamic expression of EMT-related mRNA alternative splicing variants in human mammary carcinoma (#398)

Edwin Widodo 1 2 , Kimberly Dittmar 3 , Russ P Carstens 3 , Honor Hugo 4 , Devika Gunasinghe 5 , Bryce JW van Denderen 4 , Erik W Thompson 4 5 , Eva Tomaskovic-Crook 4
  1. University of Melbourne - St. Vincent's Hospital, Fitzroy, VIC, Australia
  2. Faculty of Medicine, Brawijaya University , Malang, East Java, Indonesia
  3. School of Medicine, University of Pennsylvania , Philadelphia, USA
  4. St. Vincent's Institute, Melbourne, VIC, Australia
  5. Surgery, University of Melbourne, Melbourne, VIC, Australia

Alternative pre-messenger RNA splicing (AS) events are regulated as breast cancer cells acquire metastatic features during epithelial mesenchymal transition (EMT). We analysed splicing patterns in PMC42 human breast cancer cell line generated from Human Affymetrix Exon array data analysis using Partek Genome Suite. Validation of those variants were performed using quantitative RT-PCR in a panel of human breast cancer cell lines, including MCF7 (luminal), MDA468 (Basal A) and MDA231 (Basal B). ESRP1/2-related alternative splicings, occur in a panel of PMC42 and other human breast cancer cell lines. ESRP1 levels were higher than ESRP2, implicating ESRP1 rather than ESRP2 was the primary regulator of these AS events. Increased levels of 6 other ESRP-enhanced exons were observed (ENAH, FLNB, RALGPS2, SLK, BAIAP2, FNIP1). Other ESRP-silenced exons (OSBPL3, MAGI1, SCRIB, ARHGAP17, MBNL1) were shown reduced levels in PMC42-LA compared to PMC42-ET. We also examined the location of Zeb1, a transcription factor affecting EMT, in regulating ESRP1/2. ZEB1 knockdown in the more mesenchymal cells, PMC42-ET, increased epithelial-splicing FGFR2-IIIb exon expression. We also assessed AS of NRP1 and NRP2, VEGF co-receptors, which is independent of ESRP1 system, and found that EMT-related variants are transcripted in higher expression.