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Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer

Angiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang...

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Autores principales: Domińska, Kamila, Okła, Piotr, Kowalska, Karolina, Habrowska-Górczyńska, Dominika Ewa, Urbanek, Kinga Anna, Ochędalski, Tomasz, Piastowska-Ciesielska, Agnieszka Wanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202343/
https://www.ncbi.nlm.nih.gov/pubmed/30361641
http://dx.doi.org/10.1038/s41598-018-34049-8
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author Domińska, Kamila
Okła, Piotr
Kowalska, Karolina
Habrowska-Górczyńska, Dominika Ewa
Urbanek, Kinga Anna
Ochędalski, Tomasz
Piastowska-Ciesielska, Agnieszka Wanda
author_facet Domińska, Kamila
Okła, Piotr
Kowalska, Karolina
Habrowska-Górczyńska, Dominika Ewa
Urbanek, Kinga Anna
Ochędalski, Tomasz
Piastowska-Ciesielska, Agnieszka Wanda
author_sort Domińska, Kamila
collection PubMed
description Angiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1–7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1–7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1–7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A (VEGFA). In addition, Ang1–7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1–7 reduced the levels of estrogen receptor alpha gene (ESR1) and increased the expression of estrogen receptor beta gene (ESR2) in all prostate cancer cells; it also up-regulated androgen receptor (AR) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1–7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells.
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spelling pubmed-62023432018-10-29 Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer Domińska, Kamila Okła, Piotr Kowalska, Karolina Habrowska-Górczyńska, Dominika Ewa Urbanek, Kinga Anna Ochędalski, Tomasz Piastowska-Ciesielska, Agnieszka Wanda Sci Rep Article Angiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1–7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1–7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1–7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A (VEGFA). In addition, Ang1–7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1–7 reduced the levels of estrogen receptor alpha gene (ESR1) and increased the expression of estrogen receptor beta gene (ESR2) in all prostate cancer cells; it also up-regulated androgen receptor (AR) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1–7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells. Nature Publishing Group UK 2018-10-25 /pmc/articles/PMC6202343/ /pubmed/30361641 http://dx.doi.org/10.1038/s41598-018-34049-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Domińska, Kamila
Okła, Piotr
Kowalska, Karolina
Habrowska-Górczyńska, Dominika Ewa
Urbanek, Kinga Anna
Ochędalski, Tomasz
Piastowska-Ciesielska, Agnieszka Wanda
Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title_full Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title_fullStr Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title_full_unstemmed Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title_short Angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
title_sort angiotensin 1–7 modulates molecular and cellular processes central to the pathogenesis of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202343/
https://www.ncbi.nlm.nih.gov/pubmed/30361641
http://dx.doi.org/10.1038/s41598-018-34049-8
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