Differential expression of NAT1 pharmacogene in hormone receptor positive vs. negative female breast tumors may affect drug treatment.

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Pharmacogenetics and genomics Pub Date : 2024-09-01 Epub Date: 2024-06-03 DOI:10.1097/FPC.0000000000000540
Desislava Ivanova, Giannoulis Fakis, Sotiria Boukouvala
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引用次数: 0

Abstract

Studies have reported overexpression of NAT1 gene for xenobiotic metabolizing arylamine N -acetyltransferase type 1 in estrogen receptor positive breast tumors, and this association has been linked to patient chemoresistance and response to tamoxifen. We probed the expression of NAT1 , using quantitative reverse transcription PCR to screen clinically characterized breast cancer tissue cDNA arrays. Primers detecting all NAT1 alternative transcripts were used, and the protocol and results are reported according to consensus guidelines. The clinical information about 166 tumor samples screened is provided, including tumor stage, estrogen and progesterone receptor status and HER2 expression. NAT1 was found to be significantly ( P  < 0.001) upregulated in hormone receptor positive vs. negative tumors. No correlation was apparent between NAT1 and tumor stage or HER2 expression. Our findings demonstrate a strong correlation between the expression of NAT1 and steroid hormone receptors in breast tumors, supporting its possible utility as a pharmacogenetic biomarker or drug target. Of the two polymorphic NAT genes, NAT1 is the one primarily expressed in breast tissue, and is subjected to regulation by two differential promoters and more than one polyadenylation signal. Hormonal factors may enhance NAT1 gene expression at the transcriptional or epigenetic level, and tamoxifen has additionally been shown to inhibit NAT1 enzymatic activity. The outcome of tamoxifen treatment is also more favorable in patients with NAT1 overexpressing tumors. The study adds to the growing body of evidence implicating NAT1 in breast cancer and its pharmacological treatment.

NAT1 药基因在激素受体阳性与阴性女性乳腺肿瘤中的不同表达可能会影响药物治疗。
有研究报告称,在雌激素受体阳性的乳腺肿瘤中,异生物代谢芳胺 N-乙酰转移酶 1 型的 NAT1 基因表达过高,这种关联与患者的化疗耐药性和对他莫昔芬的反应有关。我们使用定量反转录 PCR 技术对 NAT1 的表达进行了检测,以筛选具有临床特征的乳腺癌组织 cDNA 阵列。我们使用了检测所有 NAT1 替代转录本的引物,并根据共识指南报告了实验方案和结果。报告提供了所筛选的 166 个肿瘤样本的临床信息,包括肿瘤分期、雌激素和孕激素受体状态以及 HER2 表达。结果发现,NAT1 在肿瘤中的表达明显(P
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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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