کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10814805 | 1058407 | 2015 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance
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کلمات کلیدی
XIAPFOXM1FOXPBSSurvivinTMAIAPMTT - MTTSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAchromatin immunoprecipitation - ایمن سازی کروماتینIHC - ایمونوهیستوشیمیImmunohistochemistry - ایمونوهیستوشیمیphosphate saline buffer - بافر فسفات نمکforkhead box - جعبه جعبهBreast cancer - سرطان پستانfluorescence in situ hybridization - فلورسانس در هیبریداسیون در محلFish - ماهیDrug resistance - مقاومت داروییinhibitor of apoptosis protein - مهار کننده پروتئین آپوپتوزیسTissue microarray - میکروآرشی بافتCHiP - چیپhormone receptor - گیرنده هورمون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Drug resistance is a major hurdle for successful treatment of breast cancer, the leading cause of deaths in women throughout the world. The FOXM1 transcription factor is a potent oncogene that transcriptionally regulates a wide range of target genes involved in DNA repair, metastasis, cell invasion, and migration. However, little is known about the role of FOXM1 in cell survival and the gene targets involved. Here, we show that FOXM1-overexpressing breast cancer cells display an apoptosis-resistant phenotype, which associates with the upregulation of expression of XIAP and Survivin antiapoptotic genes. Conversely, FOXM1 knockdown results in XIAP and Survivin downregulation as well as decreased binding of FOXM1 to the promoter regions of XIAP and Survivin. Consistently, FOXM1, XIAP, and Survivin expression levels were higher in taxane and anthracycline-resistant cell lines when compared to their sensitive counterparts and could not be downregulated in response to drug treatment. In agreement with our in vitro findings, we found that FOXM1 expression is significantly associated with Survivin and XIAP expression in samples from patients with IIIa stage breast invasive ductal carcinoma. Importantly, patients co-expressing FOXM1, Survivin, and nuclear XIAP had significantly worst overall survival, further confirming the physiological relevance of the regulation of Survivin and XIAP by FOXM1. Together, these findings suggest that the overexpression of FOXM1, XIAP, and Survivin contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 12, December 2015, Pages 2496-2505
Journal: Cellular Signalling - Volume 27, Issue 12, December 2015, Pages 2496-2505
نویسندگان
Gabriela Nestal de Moraes, Deborah Delbue, Karina L. Silva, Marcela Cristina Robaina, Pasarat Khongkow, Ana R. Gomes, Stefania Zona, Susanne Crocamo, André Luiz Mencalha, LÃdia M. Magalhães, Eric W.-F. Lam, Raquel C. Maia,