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Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms.
Endocr Relat Cancer 2005; 12(4):875-89ER

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.

Authors+Show Affiliations

Prostate Cancer Research Program, School of Life Sciences, Queensland University of Technology, Brisbane, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16322328

Citation

Dong, Y, et al. "Compartmentalized Expression of Kallikrein 4 (KLK4/hK4) Isoforms in Prostate Cancer: Nuclear, Cytoplasmic and Secreted Forms." Endocrine-related Cancer, vol. 12, no. 4, 2005, pp. 875-89.
Dong Y, Bui LT, Odorico DM, et al. Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. Endocr Relat Cancer. 2005;12(4):875-89.
Dong, Y., Bui, L. T., Odorico, D. M., Tan, O. L., Myers, S. A., Samaratunga, H., ... 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), pp. 875-89.
Dong Y, et al. Compartmentalized Expression of Kallikrein 4 (KLK4/hK4) Isoforms in Prostate Cancer: Nuclear, Cytoplasmic and Secreted Forms. Endocr Relat Cancer. 2005;12(4):875-89. PubMed PMID: 16322328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms. AU - Dong,Y, AU - Bui,L T, AU - Odorico,D M, AU - Tan,O L, AU - Myers,S A, AU - Samaratunga,H, AU - Gardiner,R A, AU - Clements,J A, PY - 2005/12/3/pubmed PY - 2006/3/11/medline PY - 2005/12/3/entrez SP - 875 EP - 89 JF - Endocrine-related cancer JO - Endocr. Relat. Cancer VL - 12 IS - 4 N2 - 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. SN - 1351-0088 UR - https://www.unboundmedicine.com/medline/citation/16322328/Compartmentalized_expression_of_kallikrein_4__KLK4/hK4__isoforms_in_prostate_cancer:_nuclear_cytoplasmic_and_secreted_forms_ L2 - https://erc.bioscientifica.com/doi/10.1677/erc.1.01062 DB - PRIME DP - Unbound Medicine ER -