Novel Transcript Fusion SLC45A3-ELK4 Variants in Prostate Cancer
H Cheng, SC Aisner, FD Coffman, V Fitzhugh, AM Chinnaiyan, S Cohen. UMDNJ-NJMS, Newark, NJ; University of Michigan, Ann Arbor, MI
Background: Chromosomal rearrangements and trans-splicing events that result in high level expression of erythroblast transformation–specific (ETS) gene family members are common events in human prostate cancer. Most recently, a novel ETS family fusion transcript, SLC45A3-ELK4, is identified in a subset of prostate cancer and multiple SLC45A3-ELK4 mRNA variants have been reported in both benign prostate tissue and prostate cancer. The objective of this study is to characterize SLC45A3-ELK4 mRNA variants and their expression pattern in prostate cancer.
Design: The prostate and non-prostate cancer cell lines were obtained from ATCC, with the prostate cell lines treated with or without androgen after starvation. 166 human prostate specimens were evaluated with hematoxylin and eosin (H&E) stain for cancer extent and tumor grade. RNA was isolated using TRIzol Reagent. Reverse transcription-PCR (RT-PCR) was performed using forward primers to SLC45A3 exons and a reverse primer to ELK4 exon 2. PCR products were separated and visualized on the ethidium bromide stained agarose gels and the DNA fragments corresponding to the expected sizes of fusion transcripts were sequenced.
Results: At the transcript level, we identified two novel transcript fusion SLC45A3-ELK4 variants in addition to the previously published ones. One of these variants was highly expressed in the prostate cell line VCaP and its expression level was further induced after androgen treatment. Furthermore, this variant was also detected in several human prostate cancer samples. The evaluation of the expression pattern of these SLC45A3-ELK4 variants in additional human prostate cancer samples are in process.
Conclusions: Based on the current data, we hypothesize that: 1) high expression level of ELK4 induced by androgen regulated elements plays an important role in prostate cancer development; and 2) multiple SLC45A3-ELK4 variants in the prostate cancer samples might result from trans-splicing events.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 134, Wednesday Afternoon