Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms

Dong, Y., Bui, L. T., Odorico, D. M., Tan, O. L., Myers, S. A., Samaratunga, H., Gardiner, R. A. and Clements, J. A. (2005) Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocrine-Related Cancer, 12 4: 875-889. doi:10.1677/erc.1.01062


Author Dong, Y.
Bui, L. T.
Odorico, D. M.
Tan, O. L.
Myers, S. A.
Samaratunga, H.
Gardiner, R. A.
Clements, J. A.
Title Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms
Journal name Endocrine-Related Cancer   Check publisher's open access policy
ISSN 1479-6821
1351-0088
Publication date 2005-12-01
Sub-type Article (original research)
DOI 10.1677/erc.1.01062
Volume 12
Issue 4
Start page 875
End page 889
Total pages 15
Place of publication Woodlands, Almondsbury, Bristol, UK
Publisher Society for Endocrinology
Language eng
Subject 0601 Biochemistry and Cell Biology
Abstract The prostate-specific antigen-related serine protease gene, kallikrein 4 (KLK4), is expressed in the prostate and, more importantly, overexpressed in prostate cancer. Several KLK4 mRNA splice variants have been reported, but it is still not clear which of these is most relevant to prostate cancer. Here we report that, in addition to the full-length KLK4 (KLK4-254) transcript, the exon 1 deleted KLK4 transcripts, in particular, the 5'-truncated KLK4-205 transcript, is expressed in prostate cancer. Using V5/His6 and green fluorescent protein (GFP) carboxy terminal tagged expression constructs and immunocytochemical approaches, we found that hK4-254 is cytoplasmically localized, while the N-terminal truncated hK4-205 is in the nucleus of transfected PC-3 prostate cancer cells. At the protein level, using anti-hK4 peptide antibodies specific to different regions of hK4-254 (N-terminal and C-terminal), we also demonstrated that endogenous hK4-254 (detected with the N-terminal antibody) is more intensely stained in malignant cells than in benign prostate cells, and is secreted into seminal fluid. In contrast, for the endogenous nuclear-localized N-terminal truncated hK4-205 form, there was less difference in staining intensity between benign and cancer glands. Thus, KLK4-254/hK4-254 may have utility as an immunohistochemical marker for prostate cancer. Our studies also indicate that the expression levels of the truncated KLK4 transcripts, but not KLK4-254, are regulated by androgens in LNCaP cells. Thus, these data demonstrate that there are two major isoforms of hK4 (KLK4-254/hK4-254 and KLK4-205/hK4-205) expressed in prostate cancer with different regulatory and expression profiles that imply both secreted and novel nuclear roles.
Keyword Oncology
Endocrinology & Metabolism
Tissue-specific Expression
Serine-protease Gene
Molecular-cloning
Ovarian-cancer
Family
Identification
Antigen
Variant
Roles
Immunohistochemistry
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 18:05:04 EST