Advances in prostate cancer research models:From transgenic mice to tumor xenografting models

The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.

PPARγ2 functions as a tumor suppressor in a translational mouse model of human prostate cancer

Peroxisome proliferator-activated receptorsγ(PPARγ)is a master regulator that controls energy metabolism and cell fate.PPARγ2,a PPARγisoform,is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues.In the present study,PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity.PPARγ2 was overexpressed in PC3 and LNCaP cells,and cell proliferation and migration were detected.Hematoxylin and eosin(H&E)staining was used to detect pathological changes.The genes regulated by PPARγ2 overexpression were detected by microarray analysis.The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration.PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining.We found higher mixed lineage kinase domain-like(MLKL)and lower microtubule-associated protein 1 light chain 3(LC3)expression in cancer tissues compared to controls by immunohistochemistry(IHC)staining.Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid-and energy metabolism-associated signaling pathways.These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.

Peroxisome proliferator-activated receptor gamma signaling in human sperm physiology

Peroxisome proliferator-activated receptor gamma （PPARy） is a member of the PPARs, which are transcription factors of the steroid receptor superfamily. PPARy acts as an important molecule for regulating energy homeostasis, modulates the hypothalamic-pituitary-gonadal （HPG） axis, and is reciprocally regulated by HPG. In the human, PPARγprotein is highly expressed in ejaculated spermatozoa, implying a possible role of PPARγ signaling in regulating sperm energy dissipation. PPARγ protein is also expressed in Sertoli cells and germ cells （spermatocytes）. Its activation can be induced during capacitation and the acrosome reaction. This mini-review will focus on how PPARy signaling may affect fertility and sperm quality and the potential reversibility of these adverse effects.