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Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate Cancer
Abstract
BACKGROUND: Histone deacetylase 1 (HDAC1) is a co‐repressor involved in differentiation and proliferation control. It is upregulated in malignant compared to benign tissue, and targets a number of transcription factors including p53. METHODS: By immunohistochemistry, HDAC1 protein expression was investigated in human prostate specimens and the CWR22 mouse xenograft model. Flow cytometry and deconvolution immunofluorescence were also performed. RESULTS: HDAC1 was upregulated in pre‐malignant and malignant lesions, with the highest increase in expression in hormone refractory (HR) cancer. Using the CWR22 xenograft model we showed androgen dependent regulation of HDAC1. HDAC1 overexpression led to a significant increase in proliferation and a shift towards the undifferentiated cytokeratin (CK) profile in a PC3M derivative clone constitutively expressing HDAC1. CONCLUSION: This study underlines the importance of HDAC1 in cell proliferation and the development of prostate cancer (CaP) and proposes a mechanism for HDAC1 nuclear recruitment. HDAC1 may constitute a crucial therapeutic target particularly in the most lethal phase of androgen independence. © 2004 Wiley‐Liss, Inc.
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A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Taunton, J., Hassig, C. A., & Schreiber, S. L. (1996) · Science · doi:10.1126/science.272.5260.408 · Cited by 1,829
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Anticancer activities of histone deacetylase inhibitors
Bolden, J. E., Peart, M. J., & Johnstone, R. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2133 · Cited by 2,919
Sharma, S., Kelly, T. K., & Jones, P. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp220 · Cited by 2,637
Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
Falkenberg, K. J., & Johnstone, R. W. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4360 · Cited by 1,564
Histone Deacetylase Inhibitors as Anticancer Drugs
Eckschlager, T., Plch, J., Stiborova, M., & Hrabeta, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071414 · Cited by 1,206
HDAC family: What are the cancer relevant targets?
Witt, O., Deubzer, H. E., Milde, T., & Oehme, I. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.08.016 · Cited by 1,069
Metadata
- Authors
- Halkidou, K., Gaughan, L., Cook, S., Leung, H. Y., Neal, D. E., & Robson, C. N.
- Venue
- The Prostate
- Publisher
- Wiley
- Published
- 2004-01-05
- Volume
- 59
- Issue
- 2
- Pages
- 177-189
- ISSN
- 0270-4137 (ISSN-L)
- 1097-0045
- OpenAlex
- W2090906911
- Cited by
- 509
- References
- 1
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- closed
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- Halkidou, K., Gaughan, L., Cook, S., Leung, H. Y., Neal, D. E., & Robson, C. N. (2004). Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate Cancer. The Prostate. https://doi.org/10.1002/pros.20022
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