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The Effects of Smad3 on Adrenocorticotropic Hormone-Secreting Pituitary Adenoma Development, Cell Proliferation, Apoptosis, and Hormone Secretion

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机构: [1]Capital Medical University, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing [2]Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Key Laboratory of Central Nervous System Injury Research, Capital Medical University, Beijing, China
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关键词: ACTH ACTH-Secreting pituitary adenomas Apoptosis Cell proliferation Smad3

摘要:
OBJECTIVE: Down-regulation of mothers against decapentaplegic homolog 3 (Smad3) results in the formation of tumors both in vivo and in vitro. However, little is known about the effect of Smad3 on adrenocorticotropic hormone-secreting pituitary adenomas (ACTH-PAs). Our objective was to study the expression and effect of Smad3 in ACTHPAs and its possible mechanisms. METHODS: Smad3, COOH-terminally phosphorylated mothers against decapentaplegic homolog 3 (pSmad3), and mothers against decapentaplegic homolog 2 proteins (Smad2) were detected in samples from 5 normal anterior pituitaries and 18 ACTH-PAs by Western blot and immunohistochemical analysis. Then, Smad3 expression was upregulated by Smad3-CMV plasmid or down-regulated by small interfering RNA in ACTH tumor cells (AtT-20) in vitro. Cell proliferation, apoptosis, ACTH level, and pSmad3, B-cell lymphoma/lewkmia-2 (BCL-2), and pro-opiomelanocortin (POMC) protein expression in the AtT-20 cells were measured to investigate the antitumor effects of Smad3. RESULTS: Reduced expression of Smad3 and pSmad3 but unchanged Smad2 levels were found in ACTH-PAs compared with normal pituitaries. In vitro, the overexpression of Smad3 inhibited cell proliferation, promoted cell apoptosis, and decreased ACTH secretion; in contrast, Smad3 knockdown increased cell proliferation and decreased cell apoptosis but had no significant effect on ACTH secretion. At the same time, overexpression of Smad3 increased pSmad3 but inhibited BCL-2 and POMC protein expression. On the contrary, underexpression of Smad3 inhibited pSmad3 but promoted BCL-2 and POMC protein expression. CONCLUSIONS: Smad3 is underexpressed in ACTH- PAs-Reversing the expression of Smad3 in AtT-20 cells could suppress cell growth, promote tumor apoptosis, and decrease ACTH secretion. Tumor suppression was possibly mediated by the promotion of pSmad3 and the reduction of BCL-2 and POMC expression.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 临床神经病学 3 区 外科
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 临床神经病学 4 区 外科
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出版当年[2016]版:
Q2 CLINICAL NEUROLOGY Q2 SURGERY
最新[2023]版:
Q2 SURGERY Q3 CLINICAL NEUROLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Capital Medical University, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing
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通讯机构: [2]Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Key Laboratory of Central Nervous System Injury Research, Capital Medical University, Beijing, China
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