The peripheral zone of the prostate is more prone to tumor development than the transitional zone: is the ETS family the key?
Predisposition to develop prostate cancer (PCA) varies among the prostate             zones, with the peripheral zone (PZ) more prone to tumor development than the             transitional zone (TZ). In view of the fact that molecular differences between             the zones may explain this difference, combined with the findings that translocations             between TMPRSS2 and several ETS members are frequently observed in PCA, we hypothesized             that the ETS family may be crucial to explaining this difference. Normal tissues             from the PZ and the TZ of 20 PCA patients were laser microdissected to separate             glands from stroma. Two oligo microarrays were performed in order to investigate             the variation in ETS family gene expression between the glands and the stroma             of the two zones. The ETS members, ELF-3, ELF-5, ERG, ETV-1, ETV-4, ETV-5, ETV-7             and FEV, were found to be differentially expressed. A striking observation was             that ERG and ETV-1 were found to be up-regulated in the glands of the PZ compared             to the TZ, particularly when considering that ERG and ETV-1 fusions account for             50-80% and 20% of PCA occurrences, respectively. These results indicate that the             glands and stroma of the two zones display distinct molecular differences and             zonal-specific expression of ETS members. Furthermore, ETS members up-regulated             in PCA are already overexpressed in the normal PZ, suggesting that these members             play a role in the development and progression of PCA.
Institute of Pathology, University Hospital Bonn, 53127 Bonn,                     Germany.
David
D
Adler
Andreas
A
Lindstrot
Jörg
J
Ellinger
Sebastian
S
Rogenhofer
Reinhard
R
Buettner
Sven
S
Perner
Nicolas
N
Wernert
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG