کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801748 | 1055633 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Coordinate regulation of microenvironmental stimuli and role of methylation in bone metastasis from breast carcinoma
ترجمه فارسی عنوان
تنظیم مختصری از محرک های میکرو محیطی و نقش متیلاسیون در متاستاز استخوان از کارسینوم پستان
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کلمات کلیدی
ROIRUNX2PPARγCHXSPARC5-Aza-2′-deoxycytidine - 5-Aza-2'-deoxycytidineendothelin 1 - اندوتلین 1cycloheximide - سیکلوهایسیمیدRunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2phosphatase and tensin homolog - فسفاتاز و تنسین همولوگBone metastasis - متاستاز های استخوانMethylation - متیلاسیونRegions Of Interest - مناطق مورد علاقهsecreted protein acidic and rich in cysteine - پروتئین اسیدی و غنی از سیتین را ترشح می کندPten - ژن PTENperoxisome proliferator activated receptor γ - گیرنده پروتئینزا پراکسیوم فعال γ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
The pathogenesis of bone metastasis is unclear, and much focus in metastatic biology and therapy relays on epigenetic alterations. Since DNA-methyltransferase blockade with 5-aza-2â²-deoxycytidine (dAza) counteracts tumour growth, here we utilized dAza to clarify whether molecular events undergoing epigenetic control were critical for bone metastatization. In particular, we investigated the patterns of secreted-protein acidic and rich in cysteine (SPARC) and of Endothelin 1, affected by DNA methyltransferases in tumours, with the hypothesis that in bone metastasis a coordinate function of SPARC and Endothelin 1, if any occurs, was orchestrated by DNA methylation. To this purpose, we prepared a xenograft model with the clone 1833, derived from human-MDA-MB231 cells, and dAza administration slowed-down metastasis outgrowth. This seemed consequent to the reductions of SPARC and Endothelin 1 at invasive front and in the bone marrow, mostly due to loss of Twist. In the metastasis bulk Snail, partly reduced by dAza, might sustain Endothelin 1-SPARC cooperativity. Both SPARC and Endothelin 1 underwent post-translational control by miRNAs, a molecular mechanism that might explain the in vivo data. Ectopic miR29a reduced SPARC expression also under long-term dAza exposure, while Endothelin 1 down-regulation occurred in the presence of endogenous-miR98 expression. Notably, dAza effects differed depending on in vivo and in vitro conditions. In 1833 cells exposed to 30-days dAza, SPARC-protein level was practically unaffected, while Endothelin 1 induction depended on the 3â²-UTR functionality. The blockade of methyltransferases leading to SPARC reduction in vivo, might represent a promising strategy to hamper early steps of the metastatic process affecting the osteogenic niche.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 1, January 2016, Pages 64-76
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 1, January 2016, Pages 64-76
نویسندگان
Emanuela Matteucci, Paola Maroni, Andrea Disanza, Paola Bendinelli, Maria Alfonsina Desiderio,