Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years
Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years
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DOI：
10.1186/bcr2335
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发表时间：
2009-01-01
影响因子：
7.4
通讯作者：
Harada, Nobuhiro
中科院分区：
文献类型：
--
作者：
Honma, Naoko;Takubo, Kaiyo;Harada, Nobuhiro
介绍外周定位的芳香酶，它将循环中的雄激素转化为雌激素，在绝经后乳腺癌的发病机制中起着重要作用。我们先前已经证明，老年乳腺癌(EldCa)的芳香酶mRNA水平高于对照组乳腺癌(ContCa)或正常乳腺组织。芳香酶的表达已被报道通过多个外显子1(外显子1a-1f等)的交替使用来调节；然而，外显子1在老年乳腺组织中的优先使用从未被系统地研究过。为了更好地治疗和预防EldCa，需要阐明芳香酶在老年乳腺组织中表达的调节机制。方法采用逆转录聚合酶链式反应技术检测38例老年乳腺癌患者(年龄80~99岁)乳腺组织中芳香酶基因多外显子1的使用情况，并与35例正常对照(年龄37~70岁)进行比较。芳香酶基因表达水平的比较采用单因素方差分析和Scheffe检验。结果外显子1D在老年组织中的使用频率明显高于对照组(老年组，36/38，95%vs ContCa，7/35，20%，P<；0.0001；老年人正常组织，EldNorm，30/34，88%；对照组，ContNorm，2/29，7%，P<；0.0001)。20个EldCa(53%)和12个EldNorm(35%)同时使用外显子1c和1D，但它们的优势相反(EldCa，全部1D>；1c；EldNorm，全部1c>；1D)。结论老年乳腺组织存在多个外显子1的特殊使用模式，这至少部分解释了EldCa芳香化酶水平较高的原因。这些特殊模式在衰老和致癌过程中如何发生的机制应该得到进一步的研究。
Introduction Peripherally localized aromatase, which converts circulating androgens into estrogens, is important in the pathogenesis of postmenopausal breast carcinomas. We have previously shown that aromatase mRNA levels are higher in elderly breast carcinomas (EldCa) than breast carcinomas of the control group (ContCa) or normal breast tissues. Aromatase expression has been reported to be regulated through the alternative use of multiple exons 1 (exons 1a-1f and so on); however, the preferential usage of exons 1 in elderly breast tissue has never been systematically examined. In order to properly treat and protect against EldCa, the regulation mechanism of aromatase expression in elderly breast tissues should be elucidated. The aim of the present study is to elucidate whether there are any specific patterns in use of multiple exons 1 in elderly breast tissue.Methods Usage of multiple exons 1 of the aromatase gene and mRNA levels of aromatase were examined by reverse transcription-polymerase chain reaction analysis in breast tissues of 38 elderly patients with breast cancer (age 80-99), and the results were compared with those in 35 patients of the control group (age 37-70). One-factor analysis of variance and the Scheffe test were used for the comparison of aromatase mRNA levels. Patterns of preferential utilization of multiple exons 1 of the aromatase gene were compared by chi(2) test for independence or Fisher exact test for independence using a contingency table.Results Exon 1d was utilized much more frequently in elderly tissue than in the control group irrespective of cancerous or normal tissue (EldCa, 36/38, 95% versus ContCa, 7/35, 20%, P < 0.0001; normal tissue of the elderly, EldNorm, 30/34, 88% versus normal tissue of controls, ContNorm, 2/29, 7%, P < 0.0001). Twenty EldCa (53%) and 12 EldNorm (35%) used both exons 1c and 1d; however, their dominance was reversed (EldCa, all 1d > 1c; EldNorm, all 1c > 1d).Conclusions Elderly breast tissues exhibited specific patterns in use of multiple exons 1, which at least partly explained the higher aromatase levels in EldCa. The mechanisms of how these specific patterns occur during aging and carcinogenesis should be further examined.