A transcriptional signature associated with the onset of benign prostate hyperplasia in a canine model

F. Gallardo-Arrieta, A. Doll, M. Rigau, T. Mogas, N. Juanpere, F. García, J. Morote, F. Nuñez, M. Abal, J. Lloreta, J. Reventós

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6 Citations (Scopus)

Abstract

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. Prostate 70: 1402-1412, 2010. © 2010 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)1402-1412
JournalProstate
Volume70
Issue number13
DOIs
Publication statusPublished - 15 Sep 2010

Keywords

  • Animal model
  • Benign prostatic hyperplasia
  • Clusterin
  • Dog
  • Gene-expression profiling
  • Prostate
  • TGFb

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    Gallardo-Arrieta, F., Doll, A., Rigau, M., Mogas, T., Juanpere, N., García, F., Morote, J., Nuñez, F., Abal, M., Lloreta, J., & Reventós, J. (2010). A transcriptional signature associated with the onset of benign prostate hyperplasia in a canine model. Prostate, 70(13), 1402-1412. https://doi.org/10.1002/pros.21175