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Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate Cancer
Author(s) -
Halkidou Kalipso,
Gaughan Luke,
Cook Susan,
Leung Hing Y.,
Neal David E.,
Robson Craig N.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20022
Subject(s) - downregulation and upregulation , prostate cancer , medicine , prostate , refractory (planetary science) , hormone , oncology , complication , cancer research , cancer , endocrinology , pathology , biology , gene , astrobiology , biochemistry
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.