Year-end Sale % OFF 
Abstract
The acquisition of MDR1-mediated chemoresistance poses a major obstacle to the success of conventional chemotherapeutic agents. HSF1 is also involved in chemoresistance, and several studies have demonstrated the relationship between HSF1 and MDR1 but without any consistent results. Paclitaxel- and doxorubicin-resistant cancer cells showed higher expression of MDR1 and HSF1. Depletion of HSF1 decreased mdr1 expression at mRNA level, and HSF1 directly interacted with the promoter site of mdr1, suggesting its role as a transcriptional regulator of MDR1. Phosphorylation of Ser303/307, which was involved in protein stability of HSF1 by FBXW7-mediated degradation, was found to be important for transcriptional activation of mdr1. Drug-resistant cells showed decreased expression of FBXW7, which was mediated by the activation of ERK1/2, thus indicating that over-activation of ERK1/2 in drug-resistant cells decreased FBXW7 protein stability, which finally inhibited protein degradation of pHSF1 at Ser303/307. There was a positive correlation between immunofluorescence data of pHSF1 at Ser303/307 and MDR1 in carcinogen-induced rat mammary tumors and human lung cancers. These findings identified the post-translational mechanisms of HSF1 transcription in MDR1 regulation of drug resistance development.
Highlights
Heat-shock factor 1 (HSF1) is a master regulator of the heat-shock response and facilitates cell survival and proliferation in eukaryotes
Promoter activity of mdr[1] was increased in both A549-taxolR and T47D-doxR cells when compared with their parent cells (Fig. 1d), suggesting that chemotherapeutic drug-resistant cells showed increased expression of MDR1 and HSF1; MDR1 expression was regulated at a transcriptional level and HSF1 expression at a post-translational level
In this study, HSF1 was identified as an important factor in the transcriptional activation of mdr[1], which was identified to be involved in drug resistance
Summary
Heat-shock factor 1 (HSF1) is a master regulator of the heat-shock response and facilitates cell survival and proliferation in eukaryotes. It has been widely reported that HSF1 is often overexpressed in cancer cells, suggesting that it has a role in tumorigenesis. Activation of HSF1-dependent stress response, a cytoprotective mechanism, may greatly influence the development of an adaptive and protective phenotype in cancer cells subjected to anticancer agents. Elevated expression of heat-shock proteins (HSPs) has been reported in many types of human malignancies and is reportedly associated with resistance of cancer cells to apoptosis induced by chemotherapeutic agents[1,2,3]. HSP-independent mechanisms are reportedly involved in HSF1-regulated resistance of cancer cells to chemotherapeutics[4,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
