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

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