title: Sorting nexin 5 of a new diagnostic marker of papillary thyroid carcinoma regulates Caspase-2.
abstract: Papillary thyroid carcinoma (PTC) is a well-differentiated endocrine malignant tumor that develops from thyroid follicular epithelium. The tumor represents the most common type of endocrine malignancy; however, its tumorigenesis is not fully elucidated. The aim of this study was to address the functional role of the sorting nexin (SNX) family in PTC because of recent experimental evidence suggesting that the SNX family members actively control endocytotic transportation as well as cell fate. Expression profiles of SNX family members of PTC showed a significant quantity of transcripts of SNX5. Further immunohistochemical analysis with an SNX5-specific monoclonal antibody established in this study consistently demonstrated the preferential expression of SNX5 in PTC (94.2%, 113/120 cases) as indicated by studies on 440 cases of various tumors. In contrast, other major carcinomas originating from the lung (2.6%, 1/38 cases), breast (5.1%, 2/39 cases), and intestine (4.2%, 1/24 cases) scarcely expressed SNX5. When we investigated models of murine thyroid tumors induced by the administration of carcinogens, high expression of Snx5 was also observed in well-differentiated thyroid tumors, further implying that the tumorigenesis of the thyroid gland was tightly associated with the abundance of SNX5/Snx5. Moreover epithelial cells expressing excess SNX5 showed high levels of Caspase-2 of an initiator caspase. Collectively these findings suggest that the evaluation of SNX5 expression would support pathological diagnosis of primary and secondary PTC.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shihoko
authors.initials: S
authors.lastname: Ara
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.forename: Rui Carrie
authors.initials: RC
authors.lastname: Ye
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kon
authors.forename: Tomo
authors.initials: T
authors.lastname: Honma
authors.forename: Kohji
authors.initials: K
authors.lastname: Asakura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009602:Nitrosamines / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D009602:Nitrosamines; C402667:SNX5 protein, human; D058305:Sorting Nexins; C012457:diisopropanolnitrosamine; D053143:Caspase 2