Unknown

Dataset Information

0

ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading.


ABSTRACT: High Gleason grade prostate carcinomas are aggressive, poorly differentiated tumors that exhibit diminished estrogen receptor beta (ERbeta) expression. We report that a key function of ERbeta and its specific ligand 5alpha-androstane-3beta,17beta-diol (3beta-adiol) is to maintain an epithelial phenotype and repress mesenchymal characteristics in prostate carcinoma. Stimuli (TGF-beta and hypoxia) that induce an epithelial-mesenchymal transition (EMT) diminish ERbeta expression, and loss of ERbeta is sufficient to promote an EMT. The mechanism involves ERbeta-mediated destabilization of HIF-1alpha and transcriptional repression of VEGF-A. The VEGF-A receptor neuropilin-1 drives the EMT by promoting Snail1 nuclear localization. Importantly, this mechanism is manifested in high Gleason grade cancers, which exhibit significantly more HIF-1alpha and VEGF expression, and Snail1 nuclear localization compared to low Gleason grade cancers.

SUBMITTER: Mak P 

PROVIDER: S-EPMC2881822 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2952213 | biostudies-literature
| S-EPMC2679279 | biostudies-literature
| S-EPMC2842303 | biostudies-literature
| S-EPMC309606 | biostudies-literature
| S-EPMC2928711 | biostudies-literature
| S-EPMC2673882 | biostudies-literature
| S-EPMC3018350 | biostudies-literature
| S-EPMC2764090 | biostudies-literature
| S-EPMC1544162 | biostudies-literature
| S-EPMC6089889 | biostudies-literature