| 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
(Affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.)
|
| Journal | Genes, chromosomes & cancer
(Genes Chromosomes Cancer)
Vol. 47
Issue 2
Pg. 118-26
(Feb 2008)
ISSN: 1098-2264 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 |
- Isoenzymes
- Receptors, Estrogen
- Tumor Markers, Biological
- Arylamine N-Acetyltransferase
- N-acetyltransferase 1
|
| Topics |
- Arylamine N-Acetyltransferase
(biosynthesis, genetics)
- Breast Neoplasms
(enzymology, metabolism, pathology)
- Cell Line, Tumor
- Disease Progression
- Humans
- Isoenzymes
(biosynthesis, genetics)
- Prognosis
- Receptors, Estrogen
(biosynthesis)
- Tumor Markers, Biological
(biosynthesis, genetics)
|
