| First Author | Wu WF | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 19 | Pages | E3816-E3822 |
| PubMed ID | 28439009 | Mgi Jnum | J:242223 |
| Mgi Id | MGI:5904698 | Doi | 10.1073/pnas.1702211114 |
| Citation | Wu WF, et al. (2017) Estrogen receptor beta, a regulator of androgen receptor signaling in the mouse ventral prostate. Proc Natl Acad Sci U S A 114(19):E3816-E3822 |
| abstractText | As estrogen receptor beta-/- (ERbeta-/-) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERbeta-/- mice and their WT littermates. We also treated young and old WT mice with an ERbeta-selective agonist and evaluated protein expression. The most significant findings were that ERbeta down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN). ERbeta agonist increased expression of the AR corepressor dachshund family (DACH1/2), T-cadherin, stromal caveolin-1, and nuclear PTEN and decreased expression of RAR-related orphan receptor c, Bcl2, inducible nitric oxide synthase, and IL-6. In the ERbeta-/- mouse VP, RNA sequencing revealed that the following genes were up-regulated more than fivefold: Bcl2, clusterin, the cytokines CXCL16 and -17, and a marker of basal/intermediate cells (prostate stem cell antigen) and cytokeratins 4, 5, and 17. The most down-regulated genes were the following: the antioxidant gene glutathione peroxidase 3; protease inhibitors WAP four-disulfide core domain 3 (WFDC3); the tumor-suppressive genes T-cadherin and caveolin-1; the regulator of transforming growth factor beta signaling SMAD7; and the PTEN ubiquitin ligase NEDD4. The role of ERbeta in opposing AR signaling, proliferation, and inflammation suggests that ERbeta-selective agonists may be used to prevent progression of prostate cancer, prevent fibrosis and development of benign prostatic hyperplasia, and treat prostatitis. |
