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Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer
Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, 80 Vas. Sofias Ave, 11528 Athens, Greece
* Author to whom correspondence should be addressed.
Received: 19 July 2012; in revised form: 30 August 2012 / Accepted: 10 September 2012 / Published: 12 September 2012
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.
Keywords: hsp90; breast cancer; 17-allylamino-17-demethoxygeldanamycin
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MDPI and ACS Style
Zagouri, F.; Bournakis, E.; Koutsoukos, K.; Papadimitriou, C.A. Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer. Pharmaceuticals 2012, 5, 1008-1020.
Zagouri F, Bournakis E, Koutsoukos K, Papadimitriou CA. Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer. Pharmaceuticals. 2012; 5(9):1008-1020.
Zagouri, Flora; Bournakis, Evangelos; Koutsoukos, Konstantinos; Papadimitriou, Christos A. 2012. "Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer." Pharmaceuticals 5, no. 9: 1008-1020.