HIF‐1α and HSP90: Target molecules selected from a tumorigenic papillary thyroid carcinoma cell line

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 BHP10‐3SCmice 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 BHP10‐3SCmice 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 BHP10‐3SCmice 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. (Cancer Sci 2012; 103: 464–471)