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A Closer Look at Estrogen Receptor Mutations in Breast Cancer and Their Implications for Estrogen and Antiestrogen Responses
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Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3

1
Laboratory of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, Vila Clementino, São Paulo, SP 04039-032, Brazil
2
Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP 04039-032, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Farzad Pakdel
Int. J. Mol. Sci. 2021, 22(3), 1153; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031153
Received: 27 November 2020 / Revised: 13 January 2021 / Accepted: 19 January 2021 / Published: 25 January 2021
(This article belongs to the Special Issue The Role of Estrogen Receptors in Health and Disease)
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 ERα and ERβ 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 ERα (using ERα-selective agonist PPT) and ERβ (using ERβ-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 β-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. View Full-Text
Keywords: estrogen receptor; SRC; PI3K/AKT; β-catenin; PC-3 cells estrogen receptor; SRC; PI3K/AKT; β-catenin; PC-3 cells
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MDPI and ACS Style

Lombardi, A.P.G.; Cavalheiro, R.P.; Porto, C.S.; Vicente, C.M. Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3. Int. J. Mol. Sci. 2021, 22, 1153. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031153

AMA Style

Lombardi APG, Cavalheiro RP, Porto CS, Vicente CM. Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3. International Journal of Molecular Sciences. 2021; 22(3):1153. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031153

Chicago/Turabian Style

Lombardi, Ana P.G.; Cavalheiro, Renan P.; Porto, Catarina S.; Vicente, Carolina M. 2021. "Estrogen Receptor Signaling Pathways Involved in Invasion and Colony Formation of Androgen-Independent Prostate Cancer Cells PC-3" Int. J. Mol. Sci. 22, no. 3: 1153. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031153

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