title: Additive viability-loss following hsp70/hsc70 double interference and Hsp90 inhibition in two breast cancer cell lines.
abstract: Hsp70 is an anti-apoptotic protein over-expressed in breast, lung, rectum, endometrial and bladder cancers. In this study, we investigated the impact of Hsp70 protein expression, and its close family member, Hsc70, on breast cancer cell viability and on the activity of the Hsp90/Hsp70 chaperone complex, a complex whose activity is important for the survival of cancer cells and tumours. The simultaneous blockade of Hsp70, Hsc70 and Hsp90 was most efficient in reducing breast cancer cell viability, as compared to their respective separate blockades. However, while the Hsp90 inhibition alone correlates with lost cell viability and reduced Hsp90/Hsp70 chaperone complex activity, the single or mixed reduction in Hsp70 and Hsc70 expression displayed no ability to reduce the activity of the Hsp90/Hsp70 chaperone complex. The results suggest that targeting both the Hsp70 family, as well as the Hsp90 protein will have an additive negative effect on cancer cell survival, even though their pathways of action are separate.
authors.affiliation: Department of Biomedicine, Section of Physiology, University of Bergen, N-5009 Bergen, Norway. bjarte.havik@uib.no
authors.forename: Bjarte
authors.initials: B
authors.lastname: Håvik
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bramham
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D034741:RNA, Small Interfering