Arylamine N‐acetyltransferase 1 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‐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. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2007 Wiley‐Liss, Inc.

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