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.
Wakefield
Larissa
L
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Robinson
James
J
Long
Hilary
H
Ibbitt
J Claire
JC
Cooke
Susanna
S
Hurst
Helen C
HC
Sim
Edith
E
D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011960:Receptors, Estrogen; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1