Goserelin and bicalutamide treatments alter the expression of microRNAs in the prostate.
BACKGROUND
Although endocrine therapy has been used for decades, its influence on the expression of microRNAs (miRNAs) in clinical tissue specimens has not been analyzed. Moreover, the effects of the TMPRSS2:ERG fusion on the expression of miRNAs in hormone naïve and endocrine-treated prostate cancers are poorly understood.


METHODS
We used clinical material from a neoadjuvant trial consisting of 28 men treated with goserelin (n = 8), bicalutamide (n = 9), or no treatment (n = 11) for 3 months prior to radical prostatectomy. Freshly frozen specimens were used for microarray analysis of 723 human miRNAs. Specific miRNA expression in cancer, benign epithelium and stromal tissue compartments was predicted with an in silico Bayesian modeling tool.


RESULTS
The expression of 52, 44, and 34 miRNAs was affected >1.4-fold by the endocrine treatment in the cancer, non-malignant epithelium, and stromal compartments, respectively. Of the 52 miRNAs, only 10 were equally affected by the two treatment modalities in the cancer compartment. Twenty-six of the 52 genes (50%) showed AR binding sites in their proximity in either VCaP or LNCaP cell lines. Forty-seven miRNAs were differentially expressed in TMPRSS2:ERG fusion positive compared with fusion negative cases. Endocrine treatment reduced the differences between fusion positive and negative cases.


CONCLUSIONS
Goserelin treatment and bicalutamide treatment mostly affected the expression of different miRNAs. The effect clearly varied in different tissue compartments. TMPRSS2:ERG fusion positive and negative cases showed differential expression of miRNAs, and the difference was diminished by androgen ablation.
Institute of Biomedical Technology and BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.
Saara
S
Lehmusvaara
Timo
T
Erkkilä
Alfonso
A
Urbanucci
Sanni
S
Jalava
Janne
J
Seppälä
Antti
A
Kaipia
Paula
P
Kujala
Harri
H
Lähdesmäki
Teuvo L J
TL
Tammela
Tapio
T
Visakorpi
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D050939:Gene Fusion / Q000187:drug effects; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014105:Tosyl Compounds / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000813:Anilides; D000970:Antineoplastic Agents; D035683:MicroRNAs; D009570:Nitriles; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide