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N-acetyltransferase 1 (NAT1) is an enzyme that metabolizes carcinogens, which suggests a potential role in breast carcinogenesis. High NAT1 expression in breast tumors is associated with estrogen receptor α (ER α +) and the luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ER α / ESR1 compared with normal breast tissue. There was a strong correlation between NATb promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in tumors was not the result of adipocytes, as evidenced by low perilipin ( PLIN) expression. ESR1 , NAT1 , and XBP1 expression were associated in tumor biopsies. Direct regulation of NAT1 transcription by estradiol (E 2 ) was investigated in ER α (+) MCF-7 and T47D breast cancer cells. E 2 did not increase NAT1 transcript expression but increased progesterone receptor expression in a dose-dependent manner. Likewise, NAT1 transcript levels were not increased by dihydrotestosterone (DHT) or 5 α -androstane-3 β , (3 β -adiol) 17 β -diol. Dithiothreitol increased levels of the activated, spliced XBP1 in ER α (+) MCF-7 and T47D breast cancer cells but did not affect NAT1 or ESR1 expression. We conclude that NAT1 expression is not directly regulated by E 2 , DHT, 3 β -adiol, or dithiothreitol despite high NAT1 and ESR1 expression in luminal A breast cancer cells, suggesting that ESR1 , XBP1, and NAT1 expression may share a common transcriptional network arising from the luminal epithelium associated with better survival in breast cancer. Clusters of high-expression genes, including NAT1, in breast tumors might serve as potential targets for novel therapeutic drug development.

the journal of pharmacology and experimental therapeutics/the journal of pharmacology and experimental therapeutics

High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5α-androstane-3β, 17β-Diol, or Dihydrotestosterone in Breast Cancer Cells