Associations of HSP90 Client Proteins in Human Breast Cancer

Abstract

Background: HSP90 has been studied intensively as a therapeutic target, however little is known regarding specific interactions of the large number of HSP90 client proteins. Therefore, this study investigated HSP90 client proteins sensitive to the HSP90 inhibitor geldanamycin in tumour and healthy breast tissue. Materials and Methods: Co-immunoprecipitation and SDS-PAGE were used to investigate protein interactions. Western blotting and LC-MS were used to infer protein identities. Results: HSP90 client proteins were observed in 7 out of 11 breast cancer patients. Further experiments inferred HSP40, -56/FKBP52, -60, -70, -105 and lumican to associate with HSP90 and to belong to this group of geldanamycin-sensitive proteins. In one patient, a cancer-specific group of proteins was identified. In all experiments geldanamycin resistance was observed. Conclusion: HSP90 differentially associated with client proteins and this was patient dependent. Geldanamycin resistance and lack of HSP90 client protein expression may limit clinical applications of HSP90 inhibitors.