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High N-Acetyltransferase 1 Expression Is Associated with Estrogen Receptor Expression in Breast Tumors, but Is not Under Direct Regulation by Estradiol, 5α-androstane-3ß,17ß-Diol, or Dihydrotestosterone in Breast Cancer Cells.
Zhang, Xiaoyan; Carlisle, Samantha M; Doll, Mark A; Martin, Robert C G; States, J Christopher; Klinge, Carolyn M; Hein, David W.
Afiliación
  • Zhang X; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • Carlisle SM; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • Doll MA; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • Martin RCG; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • States JC; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • Klinge CM; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
  • Hein DW; Departments of Pharmacology and Toxicology (X.Z., S.M.C., M.A.D., J.C.S., D.W.H.), Surgery (R.C.G.M.), Biochemistry and Molecular Genetics (C.M.K.), and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky d.hein@louisville.edu.
J Pharmacol Exp Ther ; 365(1): 84-93, 2018 04.
Article en En | MEDLINE | ID: mdl-29339455
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-3ß, (3ß-adiol) 17ß-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, 3ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arilamina N-Acetiltransferasa / Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Receptor alfa de Estrógeno / Isoenzimas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: J Pharmacol Exp Ther Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arilamina N-Acetiltransferasa / Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Receptor alfa de Estrógeno / Isoenzimas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: J Pharmacol Exp Ther Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos