Aromatase localization in human breast cancer tissues: Possible interactions between intratumoral stromal and parenchymal cells
Aromatase localization in human breast cancer tissues: Possible interactions between intratumoral stromal and parenchymal cells
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DOI：
10.1158/0008-5472.can-06-3105
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发表时间：
2007-04-15
期刊：
影响因子：
11.2
通讯作者：
Sasano, Hironobu
中科院分区：
文献类型：
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作者：
Miki, Yasuhiro;Suzuki, Takashi;Sasano, Hironobu
芳香化酶是绝经后乳腺癌患者通过血清雄激素转化产生雌激素所需的肿瘤内雌激素生成的关键酶。然而，关于芳香化酶在人乳腺癌组织中的肿瘤内定位一直存在争议。因此，我们首先使用激光捕获显微解剖/定量逆转录- pcr （RT-PCR）和免疫组织化学方法检测了19例乳腺癌中芳香化酶mRNA/蛋白的瘤内定位。乳腺癌组织瘤内间质细胞和实质细胞均检测到芳香酶mRNA和蛋白的表达。随后的微阵列表达谱分析和聚类分析，以及定量RT-PCR研究显示，芳香化酶和雌激素相关受体α mRNA在分离癌细胞中的表达显著正相关。我们进一步研究了从人乳腺癌组织中分离的基质细胞与乳腺癌细胞系之间的相互作用，并利用共培养系统研究了芳香化酶在癌细胞中表达的生物学特性。乳腺癌细胞系（包括MCF-7和SK-BR-3细胞）中的芳香酶mRNA和酶活性以及17 β -羟基类固醇脱氢酶1型mRNA在患者来源的32N或74T瘤内基质细胞存在下上调。类固醇转化试验的结果也与上述发现一致。我们的研究结果还表明，芳香化酶抑制剂在MCF-7中抑制共培养诱导的芳香化比在基质32N中更有效。研究芳香化酶的定位及其调控，包括人乳腺癌组织中不同细胞类型之间存在的相互作用，可能为乳腺癌患者获得更好的芳香化酶抑制剂临床疗效提供重要信息。
Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Therefore, we have first examined the intratumoral localization of aromatase mRNA/protein in 19 breast carcinomas using laser capture microdissection/quantitative reverse transcription-PCR (RT-PCR) and immunohistochemistry. Aromatase mRNA and protein were detected in both intratumoral stromal and parenchymal cells in breast carcinoma tissues. Subsequent microarray expression profiling and clustering analyses, in addition to quantitative RT-PCR studies, showed a significant positive correlation between aromatase and estrogen-related receptor alpha mRNA expression in isolated carcinoma cells. We further examined an interaction between stromal cells isolated from human breast carcinoma tissues and breast carcinoma cell lines using a coculture system to study the biological characteristic of aromatase expression in carcinoma cells. Aromatase mRNA and enzyme activity and 17 beta-hydroxysteroid dehydrogenase type 1 mRNA in breast carcinoma cell lines, including MCF-7 and SK-BR-3 cells, were up-regulated in the presence of patient-derived 32N or 74T intratumoral stromal cells. The results from steroid conversion assays were also consistent with the findings above. The results of our study also showed that aromatase inhibitors were more effective in inhibiting aromatization induced by coculture in MCF-7 than that in stromal 32N. The examination of the localization of aromatase and its regulation, including the interactions existing between different cell types in human breast carcinoma tissues, may provide important information as to achieving better clinical response to aromatase inhibitors in breast cancer patients.