Estrogen Receptors Promote Migration, Invasion and Colony Formation of the Androgen-Independent Prostate Cancer Cells PC-3 Through beta-Catenin Pathway

Autor(es)

Lombardi, Ana Paola G. ^[1] ; Vicente, Carolina M. ^[1] ; Porto, Catarina S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Farmacol, Lab Endocrinol Expt, Escola Paulista Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 11, APR 9 2020.
• Citações Web of Science: 0

Resumo

Prostate cancer is initially dependent on the androgen, gradually evolves into an androgen-independent form of the disease, also known as castration-resistant prostate cancer (CRPC). At this stage, current therapies scantily improve survival of the patient. Androgens and estrogens are involved in normal prostate and prostate cancer development. The mechanisms by which estrogens/estrogen receptors (ERs) induce prostate cancer and promote prostate cancer progression have not yet been fully identified. Our laboratory has shown that androgen-independent prostate cancer cells PC-3 express both ER alpha and ER beta. The activation of ER beta increases the expression of beta-catenin and proliferation of PC-3 cells. We now report that the activation of ER beta promotes the increase of migration, invasion and anchorage-independent growth of PC-3 cells. Furthermore, the activation of ER alpha also plays a role in invasion and anchorage-independent growth of PC-3 cells. These effects are blocked by pretreatment with PKF 118-310, compound that disrupts the complex beta-catenin/TCF/LEF, suggesting that ERs/beta-catenin are involved in all cellular characteristics of tumor development in vitro. Furthermore, PKF 118-310 also inhibited the upregulation of vascular endothelial growth factor A (VEGFA) induced by activation of ERs. VEGF also is involved on invasion of PC-3 cells. In conclusion, this study provides novel insights into the signatures and molecular mechanisms of ER beta in androgen-independent prostate cancer cells PC-3. ER alpha also plays a role on invasion and colony formation of PC-3 cells. (AU)

• Processo FAPESP: 14/05292-2 - Receptores estrogênicos e vias de sinalização intracelular envolvidas na regulação da proliferação de células do câncer testicular e do câncer prostático resistente à castração
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/16060-3 - Sinalização intracelular e função dos receptores estrogênicos em células de câncer prostático resistentes à castração e em células de câncer testicular.
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular