Kim Sun Jung, Kang Han-Sung, Chang Hye Lim, Jung Yoon Chul, Sim Hyung-Bo, Lee Keun Seok, Ro Jungsil, Lee Eun Sook
Research Institute and Hospital, National Cancer Center, Gyeonggi do 411-764, Korea.
Oncol Rep. 2008 Mar;19(3):663-8.
Arylamine N-acetyltransferase type 1 (NAT1) is reported to be involved in the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs or carcinogens. Gene-specific hypomethylation frequently occurs in a range of cancers and hypomethylation of the genes often correlates well with increased transcription levels. This study was conducted in order to evaluate the methylation status and the transcriptional activity of NAT1 in breast cancer tissues (n=72), benign breast tissues (n=31) and morphologically normal breast tissues (n=30). Our findings showed that the methylation of the NAT1 gene was identified in 39 of the breast carcinomas (54.2%), 23 normal (76.7%) and 25 benign breast tissue samples (80.6%). The breast cancer tissues showed significantly lower methylation rates of the NAT1 promoters than the normal and benign tissues (P=0.012). Furthermore, cancer tissues showed lower methylation density rates than normal and benign breast tissues (P=0.012). The tissues that showed aberrant methylation of NAT1 showed significantly less mRNA expression compared with the unmethylated cases by a thousand fold (P<0.001). Twenty cancers from the methylated group showed positive staining for the estrogen receptor (ER) (51.3%), while 72.7% from the unmethylated group stained positive (P=0.063). Our results suggest that DNA hypomethylation in the NAT1 gene appears to be present in cancerous breast tissues thus indicating that this type of methylation may significantly influence the transcriptional activation of the gene. Therefore, hypomethylation of the NAT1 gene plays a significant role in breast carcinogenesis.
据报道，1型芳胺N - 乙酰基转移酶（NAT1）参与将乙酰辅酶A的乙酰基转移至肼和芳胺类药物或致癌物的末端氮原子上。基因特异性低甲基化在一系列癌症中经常发生，并且这些基因的低甲基化通常与转录水平的升高密切相关。本研究旨在评估NAT1在乳腺癌组织（n = 72）、乳腺良性组织（n = 31）和形态学正常的乳腺组织（n = 30）中的甲基化状态和转录活性。我们的研究结果显示，在39例乳腺癌（54.2%）、23例正常乳腺组织（76.7%）和25例乳腺良性组织样本（80.6%）中检测到NAT1基因甲基化。乳腺癌组织中NAT1启动子的甲基化率显著低于正常和良性组织（P = 0.012）。此外，癌组织的甲基化密度率低于正常和良性乳腺组织（P = 0.012）。与未甲基化病例相比，显示NAT1异常甲基化的组织其mRNA表达显著降低千倍（P < 0.001）。甲基化组的20例癌症组织雌激素受体（ER）染色呈阳性（51.3%），而未甲基化组为72.7%呈阳性（P = 0.063）。我们的结果表明，NAT1基因的DNA低甲基化似乎存在于癌性乳腺组织中，这表明这种类型的甲基化可能会显著影响该基因的转录激活。因此，NAT1基因的低甲基化在乳腺癌发生过程中起重要作用。
