Utsumi T, Harada N, Maruta M, Takagi Y
Department of Surgery, School of Medicine, Fujita Health University, Aichi, Japan.
J Clin Endocrinol Metab. 1996 Jun;81(6):2344-9. doi: 10.1210/jcem.81.6.8964875.
The expression of aromatase (estrogen synthetase) is tissue specifically regulated through the alternative use of multiple exons 1 and promotors. We have determined the amounts of aromatase messenger ribonucleic acid (mRNA) and which type of multiple exons 1 of the human aromatase gene is used in breast tissues of 49 patients with breast cancer by reverse transcription-PCR analysis. The aromatase mRNA levels in these breast cancer tissues (4.53 +/- 0.66 x 10(-3) attomoles/micrograms RNA) were significantly (P < 0.01) higher than those in 16 nonmalignant breast tissues (1.73 +/- 0.40 x 10(-3) amol/micrograms RNA). Aromatase mRNA in all nonmalignant breast tissue were transcribed from skin fibroblast/fetal liver-specific exon 1 (exon 1b) of the gene. In 23 breast cancer tissues, the utilization of multiple exons 1 in the aromatase mRNA was the same as that in nonmalignant breast tissues, whereas in the other 26 cases, it changed from exon 1b to ovary-specific exon 1 (exon 1c). Such switching of tissue-specific exons 1 may affect strict regulation of the tissue-specific expression of aromatase, leading to abnormal expression of the aromatase. The consequent overproduction of local estrogen might promote carcinogenesis or the proliferation of breast cancers.
芳香化酶（雌激素合成酶）的表达通过多个1号外显子和启动子的交替使用受到组织特异性调控。我们通过逆转录-聚合酶链反应分析，测定了49例乳腺癌患者乳腺组织中芳香化酶信使核糖核酸（mRNA）的量以及人类芳香化酶基因使用的1号外显子的类型。这些乳腺癌组织中的芳香化酶mRNA水平（4.53±0.66×10⁻³阿托摩尔/微克RNA）显著高于16例非恶性乳腺组织中的水平（1.73±0.40×10⁻³阿托摩尔/微克RNA）（P<0.01）。所有非恶性乳腺组织中的芳香化酶mRNA均由该基因的皮肤成纤维细胞/胎儿肝脏特异性1号外显子（1b外显子）转录而来。在23例乳腺癌组织中，芳香化酶mRNA中1号外显子的使用情况与非恶性乳腺组织相同，而在其他26例中，其从1b外显子转变为卵巢特异性1号外显子（1c外显子）。这种组织特异性1号外显子的转换可能会影响芳香化酶组织特异性表达的严格调控，导致芳香化酶异常表达。由此产生的局部雌激素过度产生可能会促进乳腺癌的发生或增殖。
