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Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera

Oncogene volume 21, pages 7114–7120 (2002)Cite this article

Abstract

The ability to identify prostate tumor or prostate tissue specific genes that are expressed at high levels and use their protein products as targets could greatly aid in the diagnosis and treatment of prostate cancer. Using a polymerase chain reaction (PCR)-based subtraction technique, we have recovered the recently described KLK4 (prostase) gene from human prostate cDNA. In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples. Quantitative mRNA analysis also demonstrated low level expression including adrenal gland, salivary gland and thyroid. Finally, it was demonstrated that prostate cancer patient sera contain antibodies that bind specifically to recombinant KLK4 protein. This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments. The relatively specific expression profile and elevated level of KLK4 mRNA and protein in both tumor and normal prostate tissues, in addition to detectable KLK4-specific antibody in cancer patient sera, supports additional efforts to determine if KLK4 can play a role in the diagnosis of prostate cancer, the monitoring of residual disease, or act as a target for immunotherapy.

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Acknowledgements

This work is supported in part by grant CA76822 from the National Institutes of Health and by a Prostate Cancer Initiative Clinical Trials Grant from the Cancer Research Institute. Some antibodies provided in support of this work were contributed by Dr Teresa Cabezon of GlaxoSmithKline, Rixensart, Belgium. We thank Dr Thomas S Vedvick, Dr Jiangchun Xu, Sandra Koseoglu and Joe Parsons of Corixa Corporation for expert protein characterization, cDNA library construction, mRNA analysis and DNA sequencing respectively. We thank Dr Samuel Li for baculoviral recombinant protein synthesis, and Dr Darrick Carter and Charisa Cornellison for bac-protein purification, also of Corixa Corporation. Some tissue samples were obtained from the Cooperative Human Tissue Network, which is funded by the National Cancer Institute, and from the National Disease Research Interchange.

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Authors and Affiliations

  1. Corixa Corporation, 1124 Columbia Street, Suite 200, Seattle, 98104, Washington, WA, USA

    Craig H Day, Gary R Fanger, Marc W Retter, Raymond L Houghton, Xinqun Zhang, Patricia D McNeill, Martin A Cheever, Steven G Reed, Davin C Dillon & Yoshihiro Watanabe

  2. Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, New York, 14263, NY, USA

    Bonnie L Hylander & Remedios B Penetrante

  3. Hospital Aristides Maltez, Bahia, Brazil

    Aristides Maltez Filho, Marcos Nolasco & Roberto Badaro

  4. Department of Pathobiology, University of Washington, Box 357238, Seattle, 98195, Washington, WA, USA

    Steven G Reed

  5. Infectious Disease Research Institute, 1124 Columbia Street, Suite 600, Seattle, 98104, Washington, WA, USA

    Steven G Reed

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  1. Craig H Day
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  2. Gary R Fanger
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Correspondence to Craig H Day.

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Day, C., Fanger, G., Retter, M. et al. Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera. Oncogene 21, 7114–7120 (2002). https://doi.org/10.1038/sj.onc.1205786

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