Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3

Author(s)

Lombardi, Ana Paola G. ^[1] ; Cavalheiro, Renan P. ^[2] ; Porto, Catarina S. ^[1] ; Vicente, Carolina M. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Lab Expt Endocrinol, Rua Pedro Toledo 669, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biochem, BR-04039032 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 3 FEB 2021.
• Web of Science Citations: 0

Abstract

Castration-resistant prostate cancer (CRPC) is an advanced and androgen-independent form of prostate cancer. Recent studies of rapid actions mediated by estrogen in the prostate and its relationship with CRPC are emerging. We have previously shown that estrogen receptor (ER) promotes migration and invasion of the androgen-independent prostate cancer cells PC-3, but the signaling pathways involved in these events remain to be elucidated. Therefore, this study aimed to analyze the role of ER alpha and ER beta in the activation of SRC, and the involvement of SRC and PI3K/AKT on invasion and colony formation of the PC-3 cells. Our results showed that the activation of ER alpha (using ER alpha-selective agonist PPT) and ER beta (using ER beta-selective agonist DPN) increased phosphorylation of SRC in PC-3 cells. In the presence of the selective inhibitor for SRC-family kinases PP2, the effects of DPN and PPT on transmigration and soft agar colony formation assays were decreased. Furthermore, SRC is involved in the expression of the non-phosphorylated beta-catenin. Finally, using PI3K specific inhibitor Wortmannin and AKT inhibitor MK2206, we showed that PI3K/AKT are also required for invasion and colony formation of PC-3 cells simulated by ER. This study provides novel insights into molecular mechanisms of ER in PC-3 cells by demonstrating that ER, located outside the cell nucleus, activates rapid responses molecules, including SRC and PI3K/AKT, which enhance the tumorigenic potential of prostate cancer cells, increasing cell proliferation, migration, invasion, and tumor formation. (AU)

• FAPESP's process: 17/16060-3 - Intracellular signaling and role of the estrogen receptors in androgen-independent prostate cancer and testicular cancer cells.
• Grantee: Catarina Segreti Porto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/05292-2 - Estrogen receptors and intracellular signaling pathways involved in the regulation of cell proliferation of testicular cancer and castration-resistant prostate cancer
• Grantee: Catarina Segreti Porto
• Support Opportunities: Regular Research Grants