کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9892118 | 1541101 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue
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کلمات کلیدی
EGFCOUP-TF1Protein Kinase C-δRARγPKC-δERRαMTA3GRIP1cAMP responsive element binding protein 1LRH-1CREB1ERαPPARγcox2PI3 kinase - PI3 کینازaromatase - آروماتازCancer tissue - بافت سرطانیTranscriptional regulation - تنظیم ترانزیتیBreast cancer - سرطان پستانCyclooxygenase-2 - سیکلوکوکسیژناز2epidermal growth factor - عامل رشد اپیدرمیPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازliver receptor homologue-1 - همولوگ گوساله 1mitogen-activated protein kinase - پروتئین کیناز فعال با mitogenMAP kinase - کیناز MAPEstrogen receptor α - گیرنده استروژن αestrogen-related receptor - گیرنده مرتبط با استروژنperoxisome proliferator-activated receptor γ - گیرنده پروتئین کننده پروکسیوم فعال γ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue Positive and negative transcriptional regulation of aromatase expression in human breast cancer tissue](/preview/png/9892118.png)
چکیده انگلیسی
By performing primer-specific RT-PCR analyses, three laboratories including ours have found that exons I.3 and PII are the two major exon Is present in aromatase mRNAs isolated from breast tumors. These results suggest that promoters I.3 and II are the major promoters directing aromatase expression in breast tumors. The characterization of transcription factors that interact with the two elements near promoters I.3 and II, i.e., S1 and CREaro, helps us better understand the mechanism of the switch of promoter usage between normal breast tissue and cancer tissue. The positions of the two regulatory regions were mapped by DNase I footprinting and DNA deletion analyses. We applied the yeast one-hybrid approach to screen a human breast tissue hybrid cDNA expression library for genes encoding the proteins binding to these regions. Our results suggest that in normal breast tissue, the function of promoters I.3 and II is suppressed through the binding of EAR-2, COUP-TFI, and RARγ to S1, and through the binding of Snail/Slug proteins to their binding site that quenches the CREaro activity. In cancer tissue, the expression levels of EAR-2, COUP-TF1, EARγ, Snail, and Slug decrease, and aromatase expression is then up-regulated through the binding of ERRα to S1 and the binding of CREB1 or related factors to CREaro. In a separate study, we found that estrogen could up-regulate aromatase expression in breast cancer cells by a non-genomic action of ERα via cross-talk with growth factor-mediated pathways. Our preliminary results suggest that protein kinase C delta participates in this ERα-growth factor mediated regulation. To further understand the regulatory mechanism, we have recently initiated an in vivo footprinting analysis of the â260/+76 bp region of promoter I.3. The experiments were conducted with both MCF-7 and MDA-MB-231 breast cancer cells. Our results revealed several footprinted sites. Five regions (sites 1-5) were then selected for functional analysis through DNA site-directed mutagenesis experiments. This analysis has also confirmed the promoter I.3 TATA site and Snail/Slug binding site. These mutants showed higher luciferase activity when compared to the wild-type, indicating that the proteins binding to these sites were acting as repressors. By reviewing findings from our laboratory and other laboratories, a detailed mechanism for the transcriptional regulation of aromatase expression in breast cancer tissue is summarized and discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 95, Issues 1â5, May 2005, Pages 17-23
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 95, Issues 1â5, May 2005, Pages 17-23
نویسندگان
Shiuan Chen, Jingjing Ye, Ikuko Kijima, Yoshiyuki Kinoshita, Dujin Zhou,