Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling.
Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling.
复制标题
SFRP2表达减少通过上调Wnt信号传导促进垂体促肾上腺皮质激素腺瘤的发展
DOI：
10.3892/ijo.2018.4355
复制
发表时间：
2018-06
影响因子：
5.2
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Ren J;Jian F;Jiang H;Sun Y;Pan S;Gu C;Chen X;Wang W;Ning G;Bian L;Sun Q
库欣病主要由垂体促肾上腺皮质激素分泌腺瘤引起。然而，其发病机制仍不清楚。在本研究中，通过RNA测序（RNA- seq）进行全转录组分析，与正常垂体相比，促皮质性肿瘤中分泌卷曲相关蛋白2 （SFRP2）的表达降低。此外，通过逆转录-定量聚合酶链反应、western blot和免疫组织化学染色对另一组23例库欣病患者和3例正常人垂体样本进行对比，验证RNA-Seq结果，分析肿瘤组织中SFRP2的表达。临床上，SFRP2的低表达与侵袭性腺瘤的特征，包括较大的体积和侵袭性之间存在关联。相反，SFRP2过表达降低了AtT20细胞的增殖和迁移能力，并减少了体外促肾上腺皮质激素的产生。机制上，过表达的SFRP2降低了AtT20细胞细胞质和细胞核中β-catenin的水平，降低了Wnt信号活性。因此，SFRP2似乎通过调节Wnt信号通路的活性在库欣病中发挥肿瘤抑制作用。
Cushing's disease is primarily caused by pituitary adrenocorticotropin-secreting adenoma. However, its pathogenesis has remained obscure. In the present study, whole transcriptome analysis was performed by RNA sequencing (RNA-Seq) and expression of secreted frizzled-related protein 2 (SFRP2) was decreased in corticotroph tumors compared with normal pituitary glands. Furthermore, the RNA-Seq results were validated and the expression of SFRP2 in tumor tissues was analyzed by comparing another cohort of 23 patients with Cushing's disease and 3 normal human pituitary samples using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry staining. Clinically, there was an association between lower SFRP2 expression and aggressive adenoma characteristics, including larger size and invasiveness. Conversely, SFRP2 overexpression reduced the ability of AtT20 cells to proliferate and migrate, and reduced production of the adrenocorticotrophic hormone in vitro. Mechanistically, overexpressed SFRP2 reduced the level of β-catenin in the cytoplasm and nucleus, and decreased Wnt signaling activity in AtT20 cells. Therefore, SFRP2 appears to act as a tumor suppressor in Cushing's disease by regulating the activity of the Wnt signaling pathway.
登录
查看更多内容
影响因子：
29.4
作者：
Sano M;Driscoll DR;De Jesus-Monge WE;Klimstra DS;Lewis BC
通讯作者：
Lewis BC
影响因子：
11.2
作者：
Zhang Y;Morris JP 4th;Yan W;Schofield HK;Gurney A;Simeone DM;Millar SE;Hoey T;Hebrok M;Pasca di Magliano M
通讯作者：
Pasca di Magliano M
影响因子：
7
作者：
Pflueger, Dorothee;Terry, Stephane;Rubin, Mark A.
通讯作者：
Rubin, Mark A.
影响因子：
8
作者：
Nojima, M.;Suzuki, H.;Shinomura, Y.
通讯作者：
Shinomura, Y.
影响因子：
4.7
作者：
Chung, Ming-Tzeung;Lai, Hung-Cheng;Lin, Ya-Wen
通讯作者：
Lin, Ya-Wen