Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate cancer

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Research Article

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Prostate Cancer (CaP) is the second leading cause of cancer related death in USA. In human CaP, gene fusion between androgen responsive regulatory elements at the 5'-untranslated region of TMPRSS2 and ETS-related genes (ERG) is present in at least 50% of prostate tumors. Here we have investigated the unique cellular transcriptome associated with over-expression of ERG in ERG-inducible LNCaP cell model system of human CaP. Comprehensive transcriptome analyses reveal a distinct signature that distinguishes ERG dependent and independent CaP in LNCaP cells. Our data highlight a significant heterogeneity among the transcripts. Out of the 526 statistically significant differentially expressed genes, 232 genes are up-regulated and 294 genes are down-regulated in response to ERG. These ERG-associated genes are linked to several major cellular pathways, cell cycle regulation being the most significant. Consistently our data indicate that ERG plays a key role in modulating the expression of genes required for G1 to S phase transition, particularly those that affect cell cycle arrest at G1 phase. Moreover, cell cycle arrest in response to ERG appears to be promoted by induction of p21 in a p53 independent manner. These findings may provide new insights into mechanisms that promote growth and progression of CaP.

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