Year-end Sale % OFF 
Abstract
Hsp90 is an abundant protein in mammalian cells. It forms several discrete complexes, each containing distinct groups of co-chaperones that assist protein folding and refolding during stress, protein transport and degradation. It interacts with a variety of proteins that play key roles in breast neoplasia including estrogen receptors, tumor suppressor p53 protein, angiogenesis transcription factor HIF-1alpha, antiapoptotic kinase Akt, Raf-1 MAP kinase and a variety of receptor tyrosine kinases of the erbB family. Elevated Hsp90 expression has been documented in breast ductal carcinomas contributing to the proliferative activity of breast cancer cells; whilst a significantly decreased Hsp90 expression has been shown in infiltrative lobular carcinomas and lobular neoplasia. Hsp90 overexpression has been proposed as a component of a mechanism through which breast cancer cells become resistant to various stress stimuli. Therefore, pharmacological inhibition of HSPs can provide therapeutic opportunities in the field of cancer treatment. 17-allylamino,17-demethoxygeldanamycin is the first Hsp90 inhibitor that has clinically been investigated in phase II trial, yielding promising results in patients with HER2-overexpressing metastatic breast cancer, whilst other Hsp90 inhibitors (retaspimycin HCL, NVP-AUY922, NVP-BEP800, CNF2024/BIIB021, SNX-5422, STA-9090, etc.) are currently under evaluation.
Highlights
Heat shock proteins (HSP) are members of the molecular chaperones, a group of proteins that play essential role in the folding of a large number of cellular proteins [1,2]
HSPs appear to be utilized in carcinogenesis in order for cells to escape the pathways of tumour suppression, to promote progression in more advanced stage, to become treatment-resistant, and to facilitate metastasis [8]
HSP90 plays a putative role to the stability and function of a host of proteins such as BCR-ABL, HER2, epidermal growth factor receptor (EGFR), CRAF, BRAF, AKT, MET, VEGFR, FLT3, androgen and estrogen receptors, hypoxia-inducible factor (HIF)-1a, and telomerase; these protein play key roles in breast neoplasia such as growth factor independence, resistance to antigrowth signals, unlimited replicative potential, tissue invasion and metastasis, avoidance of apoptosis, and sustained angiogenesis [35,36]
Summary
Heat shock proteins (HSP) are members of the molecular chaperones, a group of proteins that play essential role in the folding of a large number of cellular proteins [1,2]. They were firstly discovered as mediators of resistance to hyperthermia [3]. Hsp is an abundant protein in mammalian cells [17] It forms several discrete complexes, each containing distinct groups of co-chaperones that assist protein folding and refolding during stress, protein transport and degradation [18]. This review article summarises the more significant points supporting the role of Hsp in breast carcinoma
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.
