Genes involved in prostate cancer invasiveness, advanced stages, and progression to metastatic disease such as PSCA, PTK6, S100B, TMPRSS4, were found up-regulated in NE-like tumors and in E2-treated OSC, together with TFF1, one of the major estrogen-regulated proteins and an indicator of estrogen receptor functionality. This evidence concerns the gene TMPRSS4 and prostate cancer.