title: HIF-1α and HSP90: target molecules selected from a tumorigenic papillary thyroid carcinoma cell line.
abstract: It is important to properly identify aggressive tumors among differentiated thyroid cancers that are most often indolent. By comparison of a tumorigenic clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell line, we looked for markers involved in the aggressive biology of thyroid cancer. Human PTC cell lines BHP10-3 and its tumorigenic subclone BHP10-3SC(mice) were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT-PCR, immunoblot analysis and immunohistochemistry in human tissue. Hypoxia-inducible factor (HIF)-1α and its chaperone protein heat shock protein (HSP)90 showed significantly increased expression in BHP10-3SC(mice) and human PTC tissue. These two genes, HIF-1α and HSP90, were further validated using siRNA gene knockdown, pharmacological inhibition using 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of both HSP90 and HIF-1α and in vivo orthotopic animal model. Invasiveness of BHP10-3SC(mice) was abrogated by blockade of HIF-1αin vitro by both siRNA and 17-AAG. The same finding was demonstrated in the orthotopic animal model. These findings support that HIF-1α is important in tumorigenesis of PTC and that it may serve to be an important target for identification and treatment of aggressive tumors.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Dankook University College of Medicine, Cheonansi, Korea.
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: Mo
authors.forename: Ik J
authors.initials: IJ
authors.lastname: Choi
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Jeong
authors.forename: Eun-Hui
authors.initials: EH
authors.lastname: Jeon
authors.forename: Soon-Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D040081:Protein Array Analysis; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering