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Cancer Genes and Genomics

Arylamine N-Acetyltransferase-1 Is Highly Expressed in Breast Cancers and Conveys Enhanced Growth and Resistance to Etoposide in Vitro

¹ Oxford Glycosciences, Abingdon, Oxon, United Kingdom;
² Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom;
³ Automated Cell Inc., Pittsburgh, PA;
⁴ Department of Surgery, Ludwig Institute for Cancer Research/University College London Breast Cancer Laboratory, London, United Kingdom; and
⁵ Department of Pharmacology, University of Oxford, Oxford, United Kingdom

Requests for reprints: Jonathan A. Terrett, Oxford Glycosciences (UK) Ltd., 10 The Quadrant, Abingdon Science Park, Abingdon, Oxon, OX14 3YS, United Kingdom. Phone: 44-1235-207687; Fax: 44-1235-207670. E-mail: jon.terrett{at}ogs.co.uk

Comparative two-dimensional proteome analysis was used to identify proteins differentially expressed in multiple clinical normal and breast cancer tissues. One protein, the expression of which was elevated in invasive ductal and lobular breast carcinomas when compared with normal breast tissue, was arylamine N-acetyltransferase-1 (NAT-1), a Phase II drug-metabolizing enzyme. NAT-1 overexpression in clinical breast cancers was confirmed at the mRNA level and immunohistochemical analysis of NAT-1 in 108 breast cancer donors demonstrated a strong association of NAT-1 staining with estrogen receptor-positive tumors. Analysis of the effect of active NAT-1 overexpression in a normal luminal epithelial-derived cell line demonstrated enhanced growth properties and etoposide resistance relative to control cells. Thus, NAT-1 may not only play a role in the development of cancers through enhanced mutagenesis but may also contribute to the resistance of some cancers to cytotoxic drugs.

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