title: Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway.
abstract: Cushing's disease is caused by pituitary corticotroph adenoma, and the pathogenesis of it has remained obscure. Here, we showed that cold inducible RNA binding protein (CIRP) was markedly elevated in corticotroph tumors. Forced overexpression of CIRP in murine AtT20 pituitary corticotroph cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, ACTH secretion and cellular proliferation. In vivo, CIRP overexpression promotes murine corticotroph tumor growth and enhances ACTH production. Mechanistically, we show that CIRP could promote AtT20 cells proliferation by inducing cyclinD1 and decreasing p27 expression via Erk1/2 signaling pathway. Clinically, CIRP overexpression is significantly correlated with Cushing's disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing's disease and its expression might be a useful biomarker for tumor recurrence.
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Jian
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Shanghai Pituitary Tumor Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Sijian
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Liuguan
authors.initials: L
authors.lastname: Bian
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Neurosurgery, Ruijin Hospital, Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Sun
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000473:pathology*; D000236:Adenoma / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D052680:Corticotrophs / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000473:pathology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C491390:CIRBP protein, human; D018809:Proliferating Cell Nuclear Antigen; D016601:RNA-Binding Proteins; C413374:p27 antigen; D019938:Cyclin D1; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cushing’s disease; Erk pathway; cold inducible RNA binding protein
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