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

• Published in: Molecular cancer research 2003-09, Vol.1 (11), p.826-835
• Main Authors: ADAM, Paul J, BERRY, Joanne, STAMPS, Alasdair C, HERATH, Athula, SIM, Edith, O'HARE, Michael J, HARRIS, Adrian L, TERRETT, Jonathan A, LOADER, Julie A, TYSON, Kerry L, CRAGGS, Graham, SMITH, Paul, DE BELIN, Jackie, STEERS, Graham, PEZZELLA, Francesco, SACHSENMEIR, Kris F
• Format: Article
• Language: English
• Subjects: Arylamine N-Acetyltransferase - genetics; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Biotechnology; Breast - cytology; Breast - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Division - drug effects; Cell Survival - drug effects; Drug Resistance, Neoplasm; Etoposide - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Gene therapy; Gynecology. Andrology. Obstetrics; Health. Pharmaceutical industry; Humans; Immunohistochemistry; Industrial applications and implications. Economical aspects; Mammary gland diseases; Medical sciences; Organ Specificity; Proteomics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Cells, Cultured; Tumors; Up-Regulation
• ISSN: 1541-7786; 1557-3125

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.