Inhibiting MAPK14 showed anti-prolactinoma effect
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RESEARCH ARTICLE
Open Access
Inhibiting MAPK14 showed antiprolactinoma effect Qiao-yan Ding1,2,3, Yu Zhang3, Li Ma1,2, Yong-gang Chen2, Jin-hu Wu1, Hong-feng Zhang4† and Xiong Wang1,2*†
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. Keywords: Prolactinoma, Prolactin, Mitogen-activated protein kinase 14, Dopamine D2 receptor
Background Pituitary tumors are a type of intracranial tumor which seriously damage human health. Pituitary adenomas are categorized based on primary cell origin and type of hormone secreted. There are prolactinoma, nonfunctional adenoma, growth hormone secreting adenoma and adrenocorticotropin-secreting adenoma [1]. The * Correspondence: [email protected] † Hong-feng Zhang and Xiong Wang contributed equally to this work. 1 Central lab, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of Wuhan, 241 Pengliuyang Road, Wuchang District, Wuhan 430060, Hubei, China 2 Department of Pharmacy, Tongren Hospital Affiliated to Wuhan University, The Third Hospital of Wuhan, Wuhan 430060, Hubei, China Full list of author information is available at the end of the article
morbidity rate of patients with pituitary tumors is 5/100, 000, of which 50% was prolactinoma [2, 3]. The tumor cells of prolactinoma secrete excess prolactin, resulting
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