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. Email:email@example.com