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Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma
Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in inva...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498590/ https://www.ncbi.nlm.nih.gov/pubmed/28680051 http://dx.doi.org/10.1038/s41598-017-04366-5 |
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author | An, Jiayin Zhang, Yin He, Jiaojiang Zang, Zhenle Zhou, Zheng Pei, Xiangdong Zheng, Xin Zhang, Weihua Yang, Hui Li, Song |
author_facet | An, Jiayin Zhang, Yin He, Jiaojiang Zang, Zhenle Zhou, Zheng Pei, Xiangdong Zheng, Xin Zhang, Weihua Yang, Hui Li, Song |
author_sort | An, Jiayin |
collection | PubMed |
description | Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA. |
format | Online Article Text |
id | pubmed-5498590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54985902017-07-10 Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma An, Jiayin Zhang, Yin He, Jiaojiang Zang, Zhenle Zhou, Zheng Pei, Xiangdong Zheng, Xin Zhang, Weihua Yang, Hui Li, Song Sci Rep Article Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3β-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3β-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA. Nature Publishing Group UK 2017-07-05 /pmc/articles/PMC5498590/ /pubmed/28680051 http://dx.doi.org/10.1038/s41598-017-04366-5 Text en © The Author(s) 2017 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 An, Jiayin Zhang, Yin He, Jiaojiang Zang, Zhenle Zhou, Zheng Pei, Xiangdong Zheng, Xin Zhang, Weihua Yang, Hui Li, Song Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title | Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title_full | Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title_fullStr | Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title_full_unstemmed | Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title_short | Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma |
title_sort | lactate dehydrogenase a promotes the invasion and proliferation of pituitary adenoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498590/ https://www.ncbi.nlm.nih.gov/pubmed/28680051 http://dx.doi.org/10.1038/s41598-017-04366-5 |
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