In prostate cancer cell lines and human umbilical vascular endothelial (HUVEC) cells, hypoxia inhibits the expression of NEP at mRNA levels; out of the three putative HREs upstream of the NEP promoter, two demonstrate a specific reduction, rather than an increase, in cobalt-induced HIF-1 binding in gel shift assays [192], suggesting a negative impact on NEP expression on the binding of HIF-1 to these HREs. Here, HIF1A is linked to Familial prostate cancer.