RNA-sequencing reveals PELP1 oncogenic functions regulate multiple pathways

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 355-388-Sex Hormone Receptor Action & Reaction
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-383
Ratna Vadlamudi*1, Monica Mann1, Yidong Chen2 and Darrell Wayne Brann3
1UTHSCSA, San Antonio, TX, 2UTHSCSA, San Antonio, 3Georgia Regents University, Augusta, GA
Proline-, glutamic- and leucine-rich protein 1 (PELP1) is a coactivator of the estrogen receptor and the dysregulation of PELP1 in hormonal cancers has been implicated in oncogenesis, metastasis and therapy resistance. Emerging findings suggest that PELP1 modulates epigenetic changes at ER target genes and  PELP1 couples ER to several signaling axes, such as Src-MAPK, PI3K-Akt. Although several aspects of PELP1 have been studied, a complete list of PELP1 target genes is not available. In this study, we have performed a whole genome analysis to profile the PELP1 transcriptome by Ilumina RNA-sequencing using a paired end sequencing assay of RNA isolated from PELP1 expressing and PELP1 knockdown breast cancer cells. The combined raw reads were aligned to the human reference genome hg19 from UCSC by TopHat. PELP1 knockdown resulted in an upregulation of 1,462 genes and 776 isoforms and downregulation of 1,248 genes and 2048 isoforms by at least two-fold compared to control PELP1 expressing cells. Gene differential expression lists were generated using DEseq and PELP1 regulated pathways were analyzed using Ingenuity Pathway Analysis (IPA). IPA analysis revealed that PELP1 modulates several pathways including molecular mechanisms of cancer, oxidative stress response, estrogen signaling, protein ubiquitination, and RNA splicing. We have validated the RNA-sequencing data by RTqPCR of genes selected from the top canonical pathways. Future analysis of the transcriptional regulation by PELP1 elucidated from the RNA-sequencing may aide in the understanding of the molecular pathogenic mechanisms underlying PELP1-mediated oncogenesis.

Nothing to Disclose: RV, MM, YC, DWB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH grant RO1 CA095681