In addition, we identified Gnetin C-induced substantial ETS2 (erythroblastosis E26 transformation-specific 2) downregulation, which is not only MTA1-dependent, but is also independent of MTA1 as a possible mechanism for the superior anticancer efficacy of Gnetin C in PCa.
We also found that the interstitial region between TMPRSS2 and ERG harbors at least one prostate tumor suppressor, ETS2, whose loss contributes to prostate cancer progression.
Among the genes over-expressed in p63-expressing carcinoma relative to usual-type adenocarcinoma were known p63-regulated genes, along with ETS2, an ETS family member previously implicated as a prostate cancer tumor suppressor gene.
Collectively, our findings established that Ets2 is a tumor suppressor gene in prostate cancer, and its loss along with other genes within the TMPRSS2-ERG interstitial region contributes to disease progression.
The consistency and magnitude of ERG overexpression in prostate cancer appeared unique, but several related ETS transcription factors were also overexpressed in matched pairs of tumor and benign samples, whereas ETS2 was significantly underexpressed.