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KiSS-1 Expression in Human Breast Cancer

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Abstract

The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using β-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3124±1262 vs 2397±1181) and significantly increased in node positive tumours compared to node negative (3637±1719 vs 2653±1994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4631±3024 vs 2280±1403) whereas expression of the receptor was reduced (480±162 vs 195±134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.

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Authors and Affiliations

  1. Metastasis & Angiogenesis Research Group, University Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, UK

    Tracey A. Martin, Gareth Watkins & Wen G. Jiang

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  1. Tracey A. Martin
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  2. Gareth Watkins
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  3. Wen G. Jiang
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Correspondence to Tracey A. Martin.

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Martin, T.A., Watkins, G. & Jiang, W.G. KiSS-1 Expression in Human Breast Cancer. Clin Exp Metastasis 22, 503–511 (2005). https://doi.org/10.1007/s10585-005-4180-0

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  • DOI: https://doi.org/10.1007/s10585-005-4180-0

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