Open AccessHIF‐1α and HSP90: Target molecules selected from a tumorigenic papillary thyroid carcinoma cell line
Author(s) -
Mo JiHun,
Choi Ik J.,
Jeong WooJin,
Jeon EunHui,
Ahn SoonHyun
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02181.x
Subject(s) - thyroid carcinoma , cancer research , carcinogenesis , biology , heat shock protein , clone (java method) , gene knockdown , cell culture , hsp90 inhibitor , thyroid cancer , immunohistochemistry , hsp90 , pathology , thyroid , cancer , medicine , gene , immunology , endocrinology , biochemistry , genetics
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‐1α in 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. ( Cancer Sci 2012; 103: 464–471)