Arylamine N-acetyltransferase 1 expression in breast cancer cell lines: a potential marker in estrogen receptor-positive tumors.

Abstract

The prognosis for patients with estrogen receptor (ER)-positive breast cancer has improved significantly with the prescription of selective ER modulators (SERMs) for ER-positive breast cancer treatment. However, only a proportion of ER-positive tumors respond to SERMs, and resistance to hormonal therapies is still a major problem. Detailed analysis of published microarray studies revealed a positive correlation between overexpression of the drug metabolizing enzyme arylamine N-acetyltransferase type 1 (NAT1) and ER positivity, and increasing evidence supports a biological role for NAT1 in breast cancer progression. We have tested a range of ER-positive and ER-negative breast cancer cell lines for NAT1 enzyme activity, and monitored promoter and polyadenylation site usage. Amongst ER-positive lines, NAT1 activities ranged from 202 +/- 28 nmol/min/mg cellular protein (ZR-75-1) to 1.8 +/- 0.4 nmol/min/mg cellular protein (MCF-7). The highest levels of NAT1 activity could not be attributed to increased NAT1 gene copy number; however, we did detect differences in NAT1 promoter and polyadenylation site usage amongst the breast tumor-derived lines. Thus, whilst all cell lines tested accumulated transcripts derived from the proximal promoter, the line expressing NAT1 most highly additionally initiated transcripts initiating at a more distal, "tissue"-specific promoter. These data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER-positive breast cancer.

• Authors: Larissa Wakefield, James Robinson, Hilary Long, J Claire Ibbitt, Susanna Cooke, Helen C Hurst, Edith Sim
• Journal: Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 47 Issue 2 Pg. 118-26 (Feb 2008) ISSN: 1098-2264 [Electronic] United States
• PMID: 17973251 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• Isoenzymes
• Receptors, Estrogen
• Arylamine N-Acetyltransferase
• N-acetyltransferase 1

Topics

• Arylamine N-Acetyltransferase (biosynthesis, genetics)
• Biomarkers, Tumor (biosynthesis, genetics)
• Breast Neoplasms (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Disease Progression
• Humans
• Isoenzymes (biosynthesis, genetics)
• Prognosis
• Receptors, Estrogen (biosynthesis)