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Hydrolysis of androgen receptor by cathepsin D: its biological significance in human prostate cancer
Author(s) -
Mordente,
; Choudhury,
Tazaki,
Mallouh,
Konno
Publication year - 1998
Publication title -
british journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 0007-1331
DOI - 10.1046/j.1464-410x.1998.00760.x
Subject(s) - lncap , prostate cancer , cathepsin , androgen receptor , cathepsin d , prostate , biochemistry , chemistry , cancer research , endogeny , cancer cell , cancer , biology , enzyme , genetics
Objective To elicit the biological role of a lysosomal protease, cathepsin D (CatD) in prostate cancer, by investigating its regulatory effect on the androgen receptor (AR) using human prostate cancer LNCaP cells and prostate tissue specimens. Materials and methods Cell extracts were prepared from LNCaP or prostate specimens by cell lysis and tissue homogenization. Proteolytic assays were performed by incubating these extracts in acidic buffer (pH 3–4) at 37°C. The resulting effects on AR and CatD were then analysed using Western immunoblots. Results The Western blots showed that AR was virtually hydrolysed with acid treatment, because endogenous CatD was activated; this activation only occurred at pH 3.2–3.5, but no specific acid appeared to be required. Further analyses suggested that CatD activation could be attributed to acid‐induced autoproteolysis of mature CatD. Similar assays were also performed on prostate tissues, including normal and malignant specimens. These studies revealed that CatD‐mediated AR hydrolysis was observed only in cancer specimens, while no such hydrolysis occurred in normal specimens. Conclusion Endogenous CatD can hydrolyse AR, thereby possibly modulating AR function/metabolism in LNCaP cells, and in cancer specimens. CatD activity also appears to differ significantly between normal and malignant tissue. Thus, CatD may play a pivotal role as a growth modulator in androgen‐dependent prostate cancer.