ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2016) 42 OC17 | DOI: 10.1530/endoabs.42.OC17

miR-32 promotes replicative changes in prostate epithelium in vivo

Leena Latonen1, Andrew Gillen1, Mira Valkonen1, Pekka Ruusuvuori1, Fuping Zhang2, Matti Poutanen2 & Tapio Visakorpi1

1Prostate Cancer Research Center and BioMediTech, University of Tampere, Finland; 2Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Finland

The androgen receptor (AR) signaling pathway is central to the emergence of castration-resistant prostate cancer (CRPC). miR-32 is an androgen regulated miRNA which is differentially expressed in CRPC compared to benign prostatic hyperplasia (BPH) and able to provide a significant growth advantage to LNCaP cells. To study how increased miR-32 expression contributes to prostate cancer formation and/or progression in vivo, we have established transgenic mice expressing miR-32 specifically in the prostate epithelium post-puberty. Expression of miR-32 transgene increases replicative activity in prostate epithelium, as demonstrated by Ki-67 staining. In aged mice, miR-32 overexpression increases incidence of goblet cell metaplasia. To provoke neoplastic lesions in prostate epithelium, the miR-32 mice were cross-bred with mice heterozygous for tumor suppressor Pten or mice overexpressing oncogenic Myc in the prostate. In both models, increase in Ki-67 staining by miR-32 overexpression was observed indicating increased replicative activity of prostate epithelium. Although incidence of PIN lesions in Pten heterozygous background was only modestly affected, the lesions with miR-32 overexpression are histologically different according to an image feature-based random forest classification. In contrast, the prostates of Myc-overexpressing mice were significantly larger when miR-32 transgene was present. Histological changes provoked by miR-32 expression in the preneoplastic lesions and tumors in the prostates of these models are presented. Our data show that miR-32 is able to affect replication potential of prostate epithelium and contribute to prostate tumor development dependently on the genetic background of the tumors.

Presenting Author: Leena Latonen BioMediTech, PL100, 33014 University of Tampere, Finland.

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