کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914792 | 1088815 | 2015 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling
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کلمات کلیدی
ALDHRXRRARAZAALDH1A1MUC4ALDH1A3MSPRetinoic acid receptor betaRetinoid X receptorHoxa1RARRES1CSCsMucin 4atRA - ATRAMethylation-specific PCR - PCR اختصاصی متیلاتaldehyde dehydrogenase - آلدئید دهیدروژنازPPRE - ارسالall-trans-retinoic acid - اسید کلرید رتینوئیکRarβ - رارRetinoic acid - رتینوئیک اسیدBreast cancer - سرطان پستانCancer stem cells - سلولهای بنیادی سرطانیTriple-negative - سه گانه منفیretinoic acid response element - عنصر پاسخ رتینوئیک اسیدperoxisome proliferator response element - عنصر پاسخ پرولیفراتور پروکسیومRARE - نادرRetinoic acid receptor - گیرنده اسید رتینوئیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Aldehyde dehydrogenase (ALDH) 1A enzymes produce retinoic acid (RA), a transcription induction molecule. To investigate if ALDH1A1 or ALDH1A3-mediated RA signaling has an active role in breast cancer tumorigenesis, we performed gene expression and tumor xenograft studies. Analysis of breast patient tumors revealed that high levels of ALDH1A3 correlated with expression of RA-inducible genes with retinoic acid response elements (RAREs), poorer patient survival and triple-negative breast cancers. This suggests a potential link between ALDH1A3 expression and RA signaling especially in aggressive and/or triple-negative breast cancers. In MDA-MB-231, MDA-MB-468 and MDA-MB-435 cells, ALDH1A3 and RA increased expression of RA-inducible genes. Interestingly, ALDH1A3 had opposing effects in tumor xenografts, increasing tumor growth and metastasis of MDA-MB-231 and MDA-MB-435 cells, but decreasing tumor growth of MDA-MB-468 cells. Exogenous RA replaced ALDH1A3 in inducing the same opposing tumor growth and metastasis effects, suggesting that ALDH1A3 mediates these effects by promoting RA signaling. Genome expression analysis revealed that ALDH1A3 induced largely divergent gene expression in MDA-MB-231 and MDA-MB-468 cells which likely resulted in the opposing tumor growth effects. Treatment with DNA methylation inhibitor 5-aza-2'deoxycytidine restored uniform RA-inducibility of RARE-containing HOXA1 and MUC4 in MDA-MB-231 and MDA-MB-468 cells, suggesting that differences in epigenetic modifications contribute to differential ALDH1A3/RA-induced gene expression in breast cancer. In summary, ALDH1A3 induces differential RA signaling in breast cancer cells which affects the rate of breast cancer progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 9, Issue 1, January 2015, Pages 17-31
Journal: Molecular Oncology - Volume 9, Issue 1, January 2015, Pages 17-31
نویسندگان
Paola Marcato, Cheryl A. Dean, Rong-Zong Liu, Krysta M. Coyle, Moamen Bydoun, Melissa Wallace, Derek Clements, Colin Turner, Edward G. Mathenge, Shashi A. Gujar, Carman A. Giacomantonio, John R. Mackey, Roseline Godbout, Patrick W.K. Lee,