The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas
Objectives. The roles of PI3K/AKT/mTOR and MAPK/ERK pathways involved in the pathogenesis of pheochromocytoma and paraganglioma (PPGL) were demonstrated mostly by in vitro studies with rat or mouse cells and were mainly studied at transcriptional level. This study aimed to investigate the effect of...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2016/5286972 |
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| author | Juan Du Anli Tong Fen Wang Yunying Cui Chunyan Li Yushi Zhang Zhaoli Yan |
| author_facet | Juan Du Anli Tong Fen Wang Yunying Cui Chunyan Li Yushi Zhang Zhaoli Yan |
| author_sort | Juan Du |
| collection | DOAJ |
| description | Objectives. The roles of PI3K/AKT/mTOR and MAPK/ERK pathways involved in the pathogenesis of pheochromocytoma and paraganglioma (PPGL) were demonstrated mostly by in vitro studies with rat or mouse cells and were mainly studied at transcriptional level. This study aimed to investigate the effect of these pathways on the proliferation of human PPGL cells and the activation of these pathways in PPGLs. Methods. Human PPGL cells were treated with sunitinib and inhibitors of PI3K (LY294002), MEK1/2 (U0126), and mTORC1/2 (AZD8055). Cell proliferation was detected by MTT assay. Protein phosphorylation was detected by Western blotting. Results. In most PPGLs, AKT, ERK1/2, and mTOR were activated. LY294002 (10 μM), U0126 (10 μM), AZD8055 (1 μM), and sunitinib (1 μM) inhibited PPGL cell proliferation in ten primary cultures of tissues, including four from patients with gene mutations. MEK1/2 inhibitor decreased mTOR phosphorylation. Inhibition of mTOR reduced phosphorylation of AKT and ERK1/2. Sunitinib inhibited phospho-ERK1/2 and phospho-mTOR. Conclusion. Our study suggested that PI3K/AKT/mTOR and MAPK/ERK signaling pathways play vital roles in human PPGL and are activated in most PPGLs. Inhibiting multiple pathways might be a novel therapeutic approach for PPGLs. |
| format | Article |
| id | doaj-art-9bb871daef034a32884b61ebd27ca657 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-9bb871daef034a32884b61ebd27ca6572025-02-03T01:33:00ZengWileyInternational Journal of Endocrinology1687-83371687-83452016-01-01201610.1155/2016/52869725286972The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human PheochromocytomasJuan Du0Anli Tong1Fen Wang2Yunying Cui3Chunyan Li4Yushi Zhang5Zhaoli Yan6Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, ChinaDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaDepartment of Endocrinology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, ChinaObjectives. The roles of PI3K/AKT/mTOR and MAPK/ERK pathways involved in the pathogenesis of pheochromocytoma and paraganglioma (PPGL) were demonstrated mostly by in vitro studies with rat or mouse cells and were mainly studied at transcriptional level. This study aimed to investigate the effect of these pathways on the proliferation of human PPGL cells and the activation of these pathways in PPGLs. Methods. Human PPGL cells were treated with sunitinib and inhibitors of PI3K (LY294002), MEK1/2 (U0126), and mTORC1/2 (AZD8055). Cell proliferation was detected by MTT assay. Protein phosphorylation was detected by Western blotting. Results. In most PPGLs, AKT, ERK1/2, and mTOR were activated. LY294002 (10 μM), U0126 (10 μM), AZD8055 (1 μM), and sunitinib (1 μM) inhibited PPGL cell proliferation in ten primary cultures of tissues, including four from patients with gene mutations. MEK1/2 inhibitor decreased mTOR phosphorylation. Inhibition of mTOR reduced phosphorylation of AKT and ERK1/2. Sunitinib inhibited phospho-ERK1/2 and phospho-mTOR. Conclusion. Our study suggested that PI3K/AKT/mTOR and MAPK/ERK signaling pathways play vital roles in human PPGL and are activated in most PPGLs. Inhibiting multiple pathways might be a novel therapeutic approach for PPGLs.http://dx.doi.org/10.1155/2016/5286972 |
| spellingShingle | Juan Du Anli Tong Fen Wang Yunying Cui Chunyan Li Yushi Zhang Zhaoli Yan The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas International Journal of Endocrinology |
| title | The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas |
| title_full | The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas |
| title_fullStr | The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas |
| title_full_unstemmed | The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas |
| title_short | The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas |
| title_sort | roles of pi3k akt mtor and mapk erk signaling pathways in human pheochromocytomas |
| url | http://dx.doi.org/10.1155/2016/5286972 |
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