Arylamine N-acetyltransferase I expression in breast cancer cell lines:: A potential marker in estrogen receptor-positive tumors

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-acetyl-transferase type I (NATI) and ER positivity, and increasing evidence supports a biological role for NATI in breast cancer progression. We have tested a range of ER-positive and ER-negative breast cancer cell lines for NATI enzyme activity, and monitored promoter and polyadenylation site usage. Amongst ER-positive lines, NATI 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 NATI activity could not be attributed to increased NATI gene copy number; however, we did detect differences in NATI 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 NATI most highly additionally initiated transcripts initiating at a more distal, "tissue"-specific promoter. These data pave the way for investigating NATI transcripts as candidate prognostic markers in ER-positive breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/ipages/1045-2257/suppmat. (c) 2007 Wiley-Liss, Inc.