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SIRT1 promotes formation of breast cancer through modulating Akt activity

The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD(+) dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate fro...

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Autores principales: Jin, Xiaoxia, Wei, Yingze, Xu, Feng, Zhao, Min, Dai, Kui, Shen, Rong, Yang, Shuyun, Zhang, Nong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995935/
https://www.ncbi.nlm.nih.gov/pubmed/29896286
http://dx.doi.org/10.7150/jca.24275
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author Jin, Xiaoxia
Wei, Yingze
Xu, Feng
Zhao, Min
Dai, Kui
Shen, Rong
Yang, Shuyun
Zhang, Nong
author_facet Jin, Xiaoxia
Wei, Yingze
Xu, Feng
Zhao, Min
Dai, Kui
Shen, Rong
Yang, Shuyun
Zhang, Nong
author_sort Jin, Xiaoxia
collection PubMed
description The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD(+) dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer.
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spelling pubmed-59959352018-06-12 SIRT1 promotes formation of breast cancer through modulating Akt activity Jin, Xiaoxia Wei, Yingze Xu, Feng Zhao, Min Dai, Kui Shen, Rong Yang, Shuyun Zhang, Nong J Cancer Research Paper The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD(+) dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer. Ivyspring International Publisher 2018-04-30 /pmc/articles/PMC5995935/ /pubmed/29896286 http://dx.doi.org/10.7150/jca.24275 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Jin, Xiaoxia
Wei, Yingze
Xu, Feng
Zhao, Min
Dai, Kui
Shen, Rong
Yang, Shuyun
Zhang, Nong
SIRT1 promotes formation of breast cancer through modulating Akt activity
title SIRT1 promotes formation of breast cancer through modulating Akt activity
title_full SIRT1 promotes formation of breast cancer through modulating Akt activity
title_fullStr SIRT1 promotes formation of breast cancer through modulating Akt activity
title_full_unstemmed SIRT1 promotes formation of breast cancer through modulating Akt activity
title_short SIRT1 promotes formation of breast cancer through modulating Akt activity
title_sort sirt1 promotes formation of breast cancer through modulating akt activity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995935/
https://www.ncbi.nlm.nih.gov/pubmed/29896286
http://dx.doi.org/10.7150/jca.24275
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