Role of TMPRSS2-ERG Gene Fusion in Negative Regulation of PSMA Expression

Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. However, it is still unclear which factors are involved in this downregulation. TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. Androgen stimulation can increase expression of the TMPRSS2-ERG fusion in fusion positive prostate cancer cells. The purpose of this investigation is to determine whether PSMA expression can be regulated by the TMPRSS2-ERG gene fusion. We employed two PSMA positive cell lines: VCaP cells, which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. After 24 hours of androgen treatment, TMPRSS2-ERG mRNA level was increased in VCaP cells. PSMA mRNA level was dramatically decreased in VCaP cells, while it only has moderate change in LNCaP cells. Treatment with the androgen antagonist flutamide partially restored PSMA expression in androgen-treated VCaP cells. Knocking down ERG by siRNA in VCaP cells enhances PSMA expression both in the presence and absence of synthetic androgen R1881. Overexpressing TMPRSS2-ERG fusions in LNCaP cells downregulated PSMA both in the presence or absence of R1881, while overexpressing wild type ERG did not. Using PSMA-based luciferase reporter assays, we found TMPRSS2-ERG fusion can inhibit PSMA activity at the transcriptional level. Our data indicated that downregulation of PSMA in androgen-treated VCaP cells appears partially mediated by TMPRSS2-ERG gene fusion

The causes of stalling fertility transitions

An examination of fertility trends in countries with multiple DHS surveys found that in the 1990s fertility stalled in mid-transition in seven countries: Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. An analysis of trends in the determinants of fertility revealed a systematic pattern of leveling off or near leveling in a number of determinants, including contraceptive use, the demand for contraception, and wanted fertility. Findings suggest no major deterioration in contraceptive access during the stall, but levels of unmet need and unwanted fertility are relatively high and improvements in access to family planning methods would therefore be desirable. No significant link was found between the presence of a stall and trends in socioeconomic development, but at the onset of the stall the level of fertility was low relative to the level of development in all but one of the stalling countries