Inhibiting MAPK14 showed anti-prolactinoma effect

Abstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and...

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Main Authors: Qiao-yan Ding, Yu Zhang, Li Ma, Yong-gang Chen, Jin-hu Wu, Hong-feng Zhang, Xiong Wang
Format: Article
Language:English
Published: BMC 2020-09-01
Series:BMC Endocrine Disorders
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12902-020-00619-z
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author Qiao-yan Ding
Yu Zhang
Li Ma
Yong-gang Chen
Jin-hu Wu
Hong-feng Zhang
Xiong Wang
author_facet Qiao-yan Ding
Yu Zhang
Li Ma
Yong-gang Chen
Jin-hu Wu
Hong-feng Zhang
Xiong Wang
author_sort Qiao-yan Ding
collection DOAJ
description Abstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer. Methods Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2 −/− ) mice models in C57BL/6 wild-type (WT), MAPK14 −/− and DRD2 −/− MAPK14+/− mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells. Results Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2 −/− MAPK14+/− mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2 −/− mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells. Conclusion These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.
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spelling doaj.art-66c415b540f343d38376cd9bb925a4682022-12-21T23:59:04ZengBMCBMC Endocrine Disorders1472-68232020-09-0120111010.1186/s12902-020-00619-zInhibiting MAPK14 showed anti-prolactinoma effectQiao-yan Ding0Yu Zhang1Li Ma2Yong-gang Chen3Jin-hu Wu4Hong-feng Zhang5Xiong Wang6Central lab, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of WuhanCollege of Pharmacy, Hubei University of Chinese MedicineCentral lab, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of WuhanDepartment of Pharmacy, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of WuhanCentral lab, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of WuhanDepartment of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyCentral lab, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of WuhanAbstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer. Methods Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2 −/− ) mice models in C57BL/6 wild-type (WT), MAPK14 −/− and DRD2 −/− MAPK14+/− mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells. Results Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2 −/− MAPK14+/− mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2 −/− mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells. Conclusion These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.http://link.springer.com/article/10.1186/s12902-020-00619-zProlactinomaProlactinMitogen-activated protein kinase 14Dopamine D2 receptor
spellingShingle Qiao-yan Ding
Yu Zhang
Li Ma
Yong-gang Chen
Jin-hu Wu
Hong-feng Zhang
Xiong Wang
Inhibiting MAPK14 showed anti-prolactinoma effect
BMC Endocrine Disorders
Prolactinoma
Prolactin
Mitogen-activated protein kinase 14
Dopamine D2 receptor
title Inhibiting MAPK14 showed anti-prolactinoma effect
title_full Inhibiting MAPK14 showed anti-prolactinoma effect
title_fullStr Inhibiting MAPK14 showed anti-prolactinoma effect
title_full_unstemmed Inhibiting MAPK14 showed anti-prolactinoma effect
title_short Inhibiting MAPK14 showed anti-prolactinoma effect
title_sort inhibiting mapk14 showed anti prolactinoma effect
topic Prolactinoma
Prolactin
Mitogen-activated protein kinase 14
Dopamine D2 receptor
url http://link.springer.com/article/10.1186/s12902-020-00619-z
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AT jinhuwu inhibitingmapk14showedantiprolactinomaeffect
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