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Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells
BACKGROUND: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and pr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009596/ https://www.ncbi.nlm.nih.gov/pubmed/27569239 http://dx.doi.org/10.4103/0366-6999.189047 |
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author | Jian, Fang-Fang Li, Yun-Feng Chen, Yu-Fan Jiang, Hong Chen, Xiao Zheng, Li-Li Zhao, Yao Wang, Wei-Qing Ning, Guang Bian, Liu-Guan Sun, Qing-Fang |
author_facet | Jian, Fang-Fang Li, Yun-Feng Chen, Yu-Fan Jiang, Hong Chen, Xiao Zheng, Li-Li Zhao, Yao Wang, Wei-Qing Ning, Guang Bian, Liu-Guan Sun, Qing-Fang |
author_sort | Jian, Fang-Fang |
collection | PubMed |
description | BACKGROUND: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). METHODS: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. RESULTS: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. CONCLUSIONS: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD. |
format | Online Article Text |
id | pubmed-5009596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-50095962016-09-14 Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells Jian, Fang-Fang Li, Yun-Feng Chen, Yu-Fan Jiang, Hong Chen, Xiao Zheng, Li-Li Zhao, Yao Wang, Wei-Qing Ning, Guang Bian, Liu-Guan Sun, Qing-Fang Chin Med J (Engl) Original Article BACKGROUND: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD). METHODS: The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. RESULTS: Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. CONCLUSIONS: Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD. Medknow Publications & Media Pvt Ltd 2016-09-05 /pmc/articles/PMC5009596/ /pubmed/27569239 http://dx.doi.org/10.4103/0366-6999.189047 Text en Copyright: © 2016 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Jian, Fang-Fang Li, Yun-Feng Chen, Yu-Fan Jiang, Hong Chen, Xiao Zheng, Li-Li Zhao, Yao Wang, Wei-Qing Ning, Guang Bian, Liu-Guan Sun, Qing-Fang Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title | Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title_full | Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title_fullStr | Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title_full_unstemmed | Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title_short | Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells |
title_sort | inhibition of ubiquitin-specific peptidase 8 suppresses adrenocorticotropic hormone production and tumorous corticotroph cell growth in att20 cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009596/ https://www.ncbi.nlm.nih.gov/pubmed/27569239 http://dx.doi.org/10.4103/0366-6999.189047 |
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