Aberrant expression of aromatase in breast cancer tissues
Aberrant expression of aromatase in breast cancer tissues
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乳腺癌组织中芳香酶的异常表达
DOI：
10.1016/s0960-0760(97)80010-6
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
N. Harada
中科院分区：
文献类型：
--
作者：
N. Harada
芳香化酶的表达通过多个外显子1和启动子的替代使用而受到组织特异性调节。我们用新开发的荧光方法分析了芳香化酶mRNA的表达水平、人类芳香化酶基因多个外显子1的优先利用以及它们的多个启动子在乳腺癌组织中的转录调控。芳香化酶mRNA在乳腺癌组织中的表达水平明显高于肿瘤远端和非恶性乳腺组织。这些非恶性组织中的芳香化酶mRNA是从皮肤成纤维细胞/胎儿肝脏特异性芳香化酶基因1 （1b外显子）转录而来。然而，在一半的乳腺癌患者中，其乳腺组织中芳香化酶mRNA的多个外显子1的利用从外显子1b变为卵巢特异性外显子1（外显子1c）。HepG2细胞和非恶性乳腺组织中的芳香酶mRNA也从外显子1b转录。然后，使用包含四个主要外显子1和启动子的新报告子，通过荧光启动子试验检测了HepG2细胞中负责外显子1b特异性利用的启动子区域。结果表明，决定细胞对1b外显子优先利用的转录元件位于1b外显子- 255 ~ - 1145的启动子区域。为了进一步研究芳香化酶mRNA表达升高的原因以及芳香化酶基因转录从1b外显子切换到1c外显子的原因，我们在培养的乳腺组织脂肪基质细胞中检测了各种因素对替代外显子1表达水平和偏好的影响。在犊牛血清存在下培养的基质细胞中，从外显子1b转录出芳香化酶mRNA。然而，去除血清或添加福斯克林或佛佛酚酯（TPA）会导致细胞中芳香化酶mRNA的快速升高，并将芳香化酶转录本切换到1c外显子，而TGFβ几乎消除了芳香化酶mRNA的表达。由于MCF-7等癌细胞的共培养增加了在含血清培养基中培养的细胞的芳香化酶mRNA，因此癌细胞可能分泌佛斯可林或TPA等刺激因子，或消耗TGFβ等血清抑制因子，从而导致芳香化酶mRNA水平升高。
The expression of aromatase is tissue-specifically regulated through the alternative use of multiple exons 1 and promoters. We analysed expression levels of aromatase mRNA, preferential utilization of multiple exon 1 of the human aromatase gene, and transcriptional regulation of their multiple promoters in breast cancer tissues by newly developed fluorometric methods. The expression levels of aromatase mRNA in breast cancer tissues were significantly higher than those in regions distal to tumours or in non-malignant breast tissues. Aromatase mRNA in these non-malignant tissues was transcribed from skin fibroblast/fetal liver-specific exon 1 (exon 1b) of the aromatase gene. However, in half the cases of breast cancer patients, the utilization of multiple exons 1 in the aromatase mRNA changed from exon 1b to ovary-specific exon 1 (exon 1c) in their breast tissues. Aromatase mRNA in HepG2 cells as well as in non-malignant breast tissues was also transcribed from exon 1b. Then, the promoter region responsible for the exon 1b-specific utilization in HepG2 cells was examined by fluorometric promoter assay using a new reporter containing four major alternative exons 1 and promoters. The results suggested that transcriptional elements determining preferential utilization of exon 1b in the cells was located on the promoter region of exon 1b from −255 to −1145. To investigate further the cause of the elevation of aromatase mRNA and the switching from exon 1b to exon 1c in the transcription of the aromatase gene, the effects of various factors on the expression levels and preference of alternative exons 1 were examined in cultured adipose stromal cells from breast tissues. Aromatase mRNA was transcribed from exon 1b in the stromal cells, cultured in the presence of calf serum. However, removal of the serum or the addition of forskolin or phorbol ester (TPA) induced a rapid elevation of aromatase mRNA and the switching of aromatase transcripts to exon 1c in the cells, whereas TGFβ almost abolished the expression of aromatase mRNA. Because co-culture of cancer cells such as MCF-7 increased aromatase mRNA of the cells cultured in the serum-containing medium, it is possible that cancer cells secret stimulatory factors acting like forskolin or TPA, or consume serum inhibitory factors acting like TGFβ, consequently causing levels of aromatase mRNA to increase.
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DOI：
10.1073/pnas.87.7.2725
发表时间：
1990-04-01
影响因子：
11.1
作者：
GILLILAND, G;PERRIN, S;BUNN, HF
通讯作者：
BUNN, HF
人类 CYP19（芳香酶）基因序列的表征，该基因介导脂肪基质细胞和胎儿肝细胞中糖皮质激素的调节。
DOI：
10.1210/mend.9.3.7776980
发表时间：
1995
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Zhao,Y;Mendelson,CR;Simpson,ER
通讯作者：
Simpson,ER
DOI：
10.1016/s0021-9258(19)36538-x
发表时间：
1993-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Mahendroo;C. Mendelson;E. Simpson;E. Simpson
通讯作者：
M. Mahendroo;C. Mendelson;E. Simpson;E. Simpson
源自人类脂肪组织的基质细胞芳香酶活性的调节。
影响因子：
4.8
作者：
Mendelson,CR;Cleland,WH;Smith,ME;Simpson,ER
通讯作者：
Simpson,ER
人 P-450AROM 的组织特异性表达。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mahendroo,MS;Means,GD;Mendelson,CR;Simpson,ER
通讯作者：
Simpson,ER