Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling

Ren,Jie; Jian,Fangfang; Jiang,Hong; Sun,Yuhao; Pan,Sijian; Gu,Changwei; Chen,Xiao; Wang,Weiqing; Ning,Guang; Bian,Liuguan; Sun,Qingfang

doi:10.3892/ijo.2018.4355

Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling

Authors:
- Jie Ren
- Fangfang Jian
- Hong Jiang
- Yuhao Sun
- Sijian Pan
- Changwei Gu
- Xiao Chen
- Weiqing Wang
- Guang Ning
- Liuguan Bian
- Qingfang Sun
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Affiliations: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Stereotactic and Functional Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Neurosurgery, Ruijin Hospital, Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: April 3, 2018 https://doi.org/10.3892/ijo.2018.4355
Pages: 1934-1946
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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