TY - JOUR T1 - High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5<em>α</em>-androstane-3<em>β</em>, 17<em>β</em>-Diol, or Dihydrotestosterone in Breast Cancer Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 84 LP - 93 DO - 10.1124/jpet.117.247031 VL - 365 IS - 1 AU - Xiaoyan Zhang AU - Samantha M. Carlisle AU - Mark A. Doll AU - Robert C. G. Martin AU - J. Christopher States AU - Carolyn M. Klinge AU - David W. Hein Y1 - 2018/04/01 UR - http://jpet.aspetjournals.org/content/365/1/84.abstract N2 - 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 (ERα+) and the luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ERα/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 (E2) was investigated in ERα (+) MCF-7 and T47D breast cancer cells. E2 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 5α-androstane-3β, (3β-adiol) 17β-diol. Dithiothreitol increased levels of the activated, spliced XBP1 in ERα (+) 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 E2, DHT, 3β-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. ER -