LABORATORY RESEARCH SMILE Upregulated by Metformin Inhibits the Function of Androgen Receptor in Prostate Cancer Cells Researchers investigated the effect and action mechanism of metformin on the function of androgen receptor (AR). Metformin was found to reduce androgen-dependent cell growth and the expression of AR target genes by inhibiting AR function in prostate cancer cells such as LNCaP and C4-2 cells. [Cancer Lett] Abstract The Prostate Basal Cell (BC) Heterogeneity and the p63-Positive BC Differentiation Spectrum in Mice Researchers report seven BC subpopulations according to their p63, cytokeratin 14 and K5 expression patterns. They discovered that these p63+ BCs contain self-renewable stem cells in culture and efficiently differentiated into luminal cells, neuroendocrine cells and BCs in the postnatal, adult and re-generating mouse prostates. [Int J Biol Sci] Full Article A Natural Androgen Receptor Antagonist Induces Cellular Senescence in Prostate Cancer Cells Scientists show that atraric acid treatment of living cells provokes molecular changes of androgen receptor (AR) signaling. In addition to a deceleration of nuclear translocation a block of the intramolecular amino/carboxy (N/C)-terminal interaction of the AR was observed. [Mol Endocrinol] Abstract Next-Generation Steroidogenesis Inhibitors, Dutasteride and Abiraterone, Attenuate but Still Do Not Eliminate Androgen Biosynthesis in 22RV1 Cells In Vitro Castration resistant prostate cancer tumors have the ability to synthesize their own androgens from cholesterol by engaging in de novo steroidogenesis. Scientists investigated the potential of 22RV1 prostate cancer cells to convert the supplemented steroid precursors within this pathway under the effects of current clinical steroidogenesis inhibitors such as abiraterone and dutasteride, either alone or in combination. [J Steroid Biochem Mol Biol] Abstract Epigenetic Regulation of EFEMP1 in Prostate Cancer: Biological Relevance and Clinical Potential Scientists sought to characterize EFEMP1 as biomarker for prostate cancer (PCa), unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. [J Cell Mol Med] Abstract Reciprocal Regulation of PCGEM1 and miR-145 Promote Proliferation of LNCaP Prostate Cancer Cells The authors speculated that reciprocal regulation of prostate cancer gene expression marker 1 (PCGEM1) and microRNA (miR)-145 promote proliferation of LNCaP prostate cancer cells. To test this hypothesis, the interaction between PCGEM1 and miR-145 was examined using a luciferase reporter assay. [J Exp Clin Cancer Res] Abstract | Full Article A Potential Regulatory Loop between Lin28B:miR-212 in Androgen-Independent Prostate Cancer Researchers found that Lin28B co-localized in the nucleus and cytoplasm of the DU145 androgen-independent prostate cancer (AIPC). The expression of Lin28B protein positively correlated with the expression of the c-Myc protein in the prostate cancer cell lines and silencing of Lin28B also correlated with a lower expression of the c-Myc protein, but not with the downregulation of c-Myc messenger RNA in the DU145 AIPC cells. [Int J Oncol] Abstract Metformin Inhibits Epithelial-Mesenchymal Transition in Prostate Cancer Cells: Involvement of the Tumor Suppressor miR30a and Its Target Gene SOX4 Researchers show that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. [Biochem Biophys Res Commun] Abstract CLINICAL RESEARCH PSA Response Rate as a Surrogate Marker for Median Overall Survival in Docetaxel-Based First-Line Treatments for Patients with Metastatic Castration-Resistant Prostate Cancer: An Analysis of 22 Trials Researchers determined the correlation between PSA response rate (PSA RR) and overall survival (OS) and identify PSA RR as a potential surrogate for OS, in docetaxel-based first-line treatments for castration-resistant prostate cancer. [Tumor Biol] Abstract A Transient Increase in Eosinophils Is Associated with Prolonged Survival in Men with Metastatic Castration-Resistant Prostate Cancer Who Receive Sipuleucel-T Scientists found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week six that resolved by week 14 in 28% of patients. This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival, and a trend in overall survival. [Cancer Immunol Res] Abstract |