ESTROGEN RECEPTOR BETA (ESR2) INCREASES THE EXPRESSION OF BETA-CATENIN IN PC-3 PROSTATE CANCER CELLS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 338-357-Steroid Hormone Actions
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-341
Ana Paola G Lombardi, Raisa Pisolato, Thais F G Lucas, Maria Fatima Magalhaes Lazari and Catarina Segreti Porto*
Universidade Federal de Sao Paulo, Sao Paulo, Brazil
Androgen deprivation is initially effective for treatment of prostate cancer, but it may lead to an androgen-independent prostate cancer (also known as castration resistant prostate cancer, CRPC) and several mechanisms have been proposed to explain that, such as alteration in the Wnt/beta-catenin signaling pathway (Cancer Res 68:9918, 2008). Recently, estrogens have been implicated as potential agents in development and progression of prostate cancer (Expert Rev Endocrinol Metab 6:437, 2011), but the role of estrogens and their classical receptors ESR1 (ERalpha) and ESR2 (ERbeta) in the CRPC is unknown. A cross-regulation between Wnt/beta-catenin, kinases, and transcriptional factors and ESR has been reported in different tissues (reviewed in Endocrine Rev 26:898, 2005). We reported the presence of ESR1 (66 kDa) and ESR2 (56 kD) in androgen-independent prostate cancer cell line PC-3. These receptors are mostly localized in the cytoplasm and plasma membrane regions, which differ from their preferential nuclear localization in normal cells, suggesting that rapid signaling pathways may be activated and modulate nuclear transcriptional events. In fact, the treatment with ESR2-selective agonist DPN (10 nM) for 30 min, 1 and 2 hours increases the expression of β-catenin in the cytosolic fraction of PC-3 cells. These data were confirmed by immunofluorescence assays. Furthermore, DPN increases the expression of cyclin D2 and this effect is inhibited by PKF118-310, that selectively disrupts beta-catenin-TCF (T cell factor), suggesting that beta-catenin is involved in the regulation of cyclin D2 expression. The mechanisms involved in the regulation of beta-catenin expression by estrogen receptors and the role of this protein in the androgen-independent prostate cancer must be better elucidated.

Nothing to Disclose: APGL, RP, TFGL, MFML, CSP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: FAPESP, CAPES and CNPq