Wakefield, L., Robinson, J., Long, H., Ibbitt, J. C., Cooke, S. , Hurst, H. C. and Sim, E. (2008) Arylamine N-acetyltransferase 1 expression in breast cancer cell lines: A potential marker in estrogen receptor-positive tumors. Genes, Chromosomes and Cancer, 47(2), pp. 118-126. (doi: 10.1002/gcc.20512) (PMID:17973251)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cooke, Dr Susie |
| Authors: | Wakefield, L., Robinson, J., Long, H., Ibbitt, J. C., Cooke, S., Hurst, H. C., and Sim, E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Genes, Chromosomes and Cancer |
| Publisher: | Wiley |
| ISSN: | 1045-2257 |
| ISSN (Online): | 1098-2264 |
| Published Online: | 31 October 2007 |
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