A transcriptional signature associated with the onset of benign prostate hyperplasia in a canine model.
BACKGROUND
Benign prostatic hyperplasia (BPH) represents the most frequent proliferative abnormality of the human prostate. In spite of the well-characterized architectural development of BPH, little is known about the cellular and molecular events that contribute to it.


METHODS
We have developed an animal model to evaluate the follow-up of hormone-induced BPH and the analysis of the gene expression associated with BPH. Immunohistochemistry on human patient samples validated the BPH-related molecular alterations.


RESULTS
Canine specific Affymetrix microarray analysis performed on sequential biopsies obtained from a beagle dog dynamic model characterized a number of genes altered during the onset of BPH. In addition to the genes involved in calcification, matrix remodeling, detoxification, cell movement, and mucosa protection (MGP, MMP2, TIMP2, ITIH3, GST, MT2A, SULT1A1, FKBP1B, MUC1, STRBP, TFF3), the up-regulation of TGFB3 and CLU indicated a complete adjustment of the transdifferentiation, senescence and apoptosis programs. The up-regulation of Clusterin was validated by RT-qPCR and immunohistochemistry, both in the dog dynamic model and in human samples, further confirming the suitability of the animal model for the study of the molecular alterations associated with BPH.


CONCLUSIONS
Transcriptome analysis performed on a dynamic animal model that accurately mimicked the human clinic, allowed us to characterize a gene expression pattern associated with the onset of BPH.
Gallardo-Arrieta
F
F
Veterinary Faculty, Departament of Medicine and Animal Surgery, Autonomous University of Barcelona, Spain.
Doll
A
A
Rigau
M
M
Mogas
T
T
Juanpere
N
N
García
F
F
Morote
J
J
Nuñez
F
F
Abal
M
M
Lloreta
J
J
Reventós
J
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051152:Clusterin