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https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#1
J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28282036/heterarchy-of-transcription-factors-driving-basal-and-luminal-cell-phenotypes-in-human-urothelium
#2
Carl Fishwick, Janet Higgins, Lawrence Percival-Alwyn, Arianna Hustler, Joanna Pearson, Sarah Bastkowski, Simon Moxon, David Swarbreck, Chris D Greenman, Jennifer Southgate
Cell differentiation is affected by complex networks of transcription factors that co-ordinate re-organisation of the chromatin landscape. The hierarchies of these relationships can be difficult to dissect. During in vitro differentiation of normal human uro-epithelial cells, formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and RNA-seq was used to identify alterations in chromatin accessibility and gene expression changes following activation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) as a differentiation-initiating event...
March 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28273452/enhancer-mediated-oncogenic-function-of-the-menin-tumor-suppressor-in-breast-cancer
#3
Koen M A Dreijerink, Anna C Groner, Erica S M Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y Lin, Wouter de Laat, Prakash K Rao, Henry W Long, Myles Brown
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER(+) cells...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28270510/down-regulation-of-forkhead-box-protein-a1-foxa1-leads-to-cancer-stem-cell-like-properties-in-tamoxifen-resistant-breast-cancer-cells-through-induction-of-interleukin-6
#4
Noritaka Yamaguchi, Yuji Nakayama, Naoto Yamaguchi
The selective estrogen receptor (ER) modulator tamoxifen inhibits ER signaling in breast cancer cells, and it is used for the treatment of ER-positive breast cancer. However, this type of cancer often acquires resistance to tamoxifen, and a better understanding of the molecular mechanisms underlying tamoxifen-resistance is required. In this study, we established tamoxifen-resistant (TAM-R) breast cancer cells by long-term tamoxifen treatment of ER-positive breast cancer MCF7 cells. In TAM-R cells, expression of not only ERα, a major form of ER in breast cancer, but also its transcriptional partner forkhead box protein A1 (FOXA1) was found to be reduced...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28264478/crosstalk-of-the-androgen-receptor-with-transcriptional-collaborators-potential-therapeutic-targets-for-castration-resistant-prostate-cancer
#5
REVIEW
Daisuke Obinata, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC)...
February 28, 2017: Cancers
https://www.readbyqxmd.com/read/28261581/pbx1-as-pioneer-factor-a-case-still-open
#6
REVIEW
Britta M Grebbin, Dorothea Schulte
Pioneer factors are proteins that can recognize their target sites in barely accessible chromatin and initiate a cascade of events that allows for later transcriptional activation of the respective genes. Pioneer factors are therefore particularly well-suited to initiate cell fate changes. To date, only a small number of pioneer factors have been identified and studied in depth, such as FOXD3/FOXA1, OCT4, or SOX2. Interestingly, several recent studies reported that the PBC transcription factor PBX1 can access transcriptionally inactive genomic loci...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28255498/identification-of-nurr1-exon-4-and-foxa1-exon-3-haplotypes-associated-with-mrna-expression-levels-in-peripheral-blood-lymphocytes-of-parkinson-s-patients-in-small-indian-population
#7
Jayakrishna Tippabathani, Jayshree Nellore, Vaishnavie Radhakrishnan, Somashree Banik, Sonia Kapoor
Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson's patients (PD) with anti-PD medications (20 males aged 65.85 ± 1.19 and 10 females aged 65.7 ± 1.202) and 30 age matched healthy people (20 males aged 68.45 ± 1.282 and 10 females aged 65.8 ± 1.133) were included. The expression of NURR1 and FOXA1 in PBL was detected by Q-PCR and haplotypes were identified by PCR-SSCP...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28238418/foxa1-is-expressed-in-ovarian-mucinous-neoplasms
#8
Georgia Karpathiou, Melany Venet, Mousa Mobarki, Fabien Forest, Celine Chauleur, Michel Peoc'h
FOXA1 is a transcription factor essential for the binding and action of other transcription factors on the chromatin. It is the major regulator of endoderm differentiation. It has important roles in breast, prostate and endometrial cancer. It has never been studied in ovarian tumours. The aim of this study was to investigate its expression in ovarian epithelial neoplasms. A total of 195 primary ovarian epithelial borderline or malignant tumours were immunohistochemically studied for the expression of FOXA1...
February 23, 2017: Pathology
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#9
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28209524/foxa1-in-hpv-associated-carcinomas-its-expression-in-carcinomas-of-the-head-and-neck-and-of-the-uterine-cervix
#10
Georgia Karpathiou, Vanessa Da Cruz, Francois Casteillo, Mousa Mobarki, Jean Marc Dumollard, Celine Chauleur, Fabien Forest, Jean Michel Prades, Michel Peoc'h
BACKGROUND: FOXA1 is a major transcription factor involved in the action of human papilloma virus (HPV). However, it has been never studied in HPV-associated tumors. AIM OF THE STUDY: To investigate its expression in cervical and head and neck tumors. MATERIAL AND METHODS: 63 cervical carcinomas/dysplasias and 152 head and neck squamous cell carcinomas (HNSCC) were immunohistochemically studied for the expression of FOXA1. RESULTS: 63...
February 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28105112/microrna-212-targets-foxa1-and-suppresses-the-proliferation-and-invasion-of-intrahepatic-cholangiocarcinoma-cells
#11
Lei Zhu, Feizhou Huang, Gang Deng, Wanpin Nie, Wei Huang, Hongbo Xu, Shaopeng Zheng, Zhongjie Yi, Tao Wan
MicroRNAs (miRNAs), which are a class of small RNAs, have been shown to negatively regulate the expression of their target genes by directly binding to the 3'-untranslated region (3'-UTR) of mRNA. miRNA dysregulation has been associated with the pathogenesis of numerous types of human cancer. However, the role of miRNAs in intrahepatic cholangiocarcinoma (ICC) has yet to be fully elucidated. The present study aimed to investigate the role of miR-212 in the growth and metastasis of ICC in vitro, as well as the underlying mechanism...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101191/microrna-212-suppresses-the-proliferation-and-migration-of-osteosarcoma-cells-by-targeting-forkhead-box-protein-a1
#12
Jian Liu, Bohua Chen, Bin Yue, Junde Yang
MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting the 3' untranslated region (UTR) of mRNA, causing translational repression or mRNA degradation. Deregulation of specific miRNAs, including miR-212, has been identified in patients with osteosarcoma. However, the underlying mechanism is yet to be fully elucidated. The present study aimed to reveal the regulatory mechanism of miR-212 in osteosarcoma cell viability and migration. Quantitative polymerase chain reaction data revealed that miR-212 was significantly downregulated in osteosarcoma tissues compared with normal bone tissues...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28038451/androgen-receptor-transcriptionally-regulates-semaphorin-3c-in-a-gata2-dependent-manner
#13
Kevin J Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Shahram Khosravi, Parvin Yenki, Charan Tse, James W Peacock, Aishwariya Sharma, Yan Ting Chiang, Yuzhuo Wang, Artem Cherkasov, Paul S Rennie, Martin E Gleave, Christopher J Ong
The androgen receptor (AR) is a member of the nuclear receptor superfamily of transcription factors and is central to prostate cancer (PCa) progression. Ligand-activated AR engages androgen response elements (AREs) at androgen-responsive genes to drive the expression of gene batteries involved in cell proliferation and cell fate. Understanding the transcriptional targets of the AR has become critical in apprehending the mechanisms driving treatment-resistant stages of PCa. Although AR transcription regulation has been extensively studied, the signaling networks downstream of AR are incompletely described...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27997592/identification-of-post-transcriptional-modulators-of-breast-cancer-transcription-factor-activity-using-mindy
#14
Thomas M Campbell, Mauro A A Castro, Bruce A J Ponder, Kerstin B Meyer
We have recently identified transcription factors (TFs) that are key drivers of breast cancer risk. To better understand the pathways or sub-networks in which these TFs mediate their function we sought to identify upstream modulators of their activity. We applied the MINDy (Modulator Inference by Network Dynamics) algorithm to four TFs (ESR1, FOXA1, GATA3 and SPDEF) that are key drivers of estrogen receptor-positive (ER+) breast cancer risk, as well as cancer progression. Our computational analysis identified over 500 potential modulators...
2016: PloS One
https://www.readbyqxmd.com/read/27974698/genome-wide-copy-number-analyses-of-superficial-esophageal-squamous-cell-carcinoma-with-and-without-metastasis
#15
Pengjiao Wang, Ling Shan, Liyan Xue, Bo Zheng, Jianming Ying, Ning Lu
Superficial esophageal squamous cell carcinoma (ESCC) is generally considered a subtype of less invasive ESCC. Yet a subset of these superficial ESCC would have metastasis after esophagostomy or endoscopic resection and lead to poor prognosis. The objective of this study is to determine biomarkers that can identify such subset of superficial ESCC that would have metastasis after surgery using genome wide copy number alteration (CNA) analyses. The CNAs of 38 cases of superficial ESCCs originated from radical surgery, including 19 without metastasis and 19 with metastasis within 5 years' post-surgery, were analyzed using Affymetrix OncoScan™ FFPE Assay...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27959926/predictors-of-chemosensitivity-in-triple-negative-breast-cancer-an-integrated-genomic-analysis
#16
Tingting Jiang, Weiwei Shi, Vikram B Wali, Lőrinc S Pongor, Charles Li, Rosanna Lau, Balázs Győrffy, Richard P Lifton, William F Symmans, Lajos Pusztai, Christos Hatzis
BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. METHODS AND FINDINGS: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27934886/foxa1-is-essential-for-development-and-functional-integrity-of-the-subthalamic-nucleus
#17
Emanuel Gasser, Helge C Johannssen, Thomas Rülicke, Hanns Ulrich Zeilhofer, Markus Stoffel
Inactivation of transcription factor Foxa1 in mice results in neonatal mortality of unknown cause. Here, we report that ablation of Foxa1 causes impaired development and loss of the subthalamic nucleus (STN). Functional deficits in the STN have been implicated in the etiology of Huntington's and Parkinson's disease. We show that neuronal ablation by Synapsin1-Cre-mediated Foxa1 deletion is sufficient to induce hyperlocomotion in mice. Transcriptome profiling of STN neurons in conditional Foxa1 knockout mice revealed changes in gene expression reminiscent of those in neurodegenerative diseases...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926873/foxa1-directs-h3k4-monomethylation-at-enhancers-via-recruitment-of-the-methyltransferase-mll3
#18
Kamila M Jozwik, Igor Chernukhin, Aurelien A Serandour, Sankari Nagarajan, Jason S Carroll
FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells and found histone-lysine N-methyltransferase (MLL3) as the top FOXA1-interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition. We performed MLL3 chromatin immunoprecipitation sequencing (ChIP-seq) in breast cancer cells, and MLL3 was shown to occupy regions marked by FOXA1 occupancy and H3K4me1 and H3K4me2...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#19
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2-negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER(+) /HER2(-) ) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER(+) /HER2(-) NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair...
February 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27924948/foxa1-gata3-and-ppar%C3%A9-cooperate-to-drive-luminal-subtype-in-bladder-cancer-a-molecular-analysis-of-established-human-cell-lines
#20
Joshua I Warrick, Vonn Walter, Hironobu Yamashita, Eunah Chung, Lauren Shuman, Vasty Osei Amponsa, Zongyu Zheng, Wilson Chan, Tiffany L Whitcomb, Feng Yue, Tejaswi Iyyanki, Yuka I Kawasawa, Matthew Kaag, Wansong Guo, Jay D Raman, Joo-Seop Park, David J DeGraff
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA)...
December 7, 2016: Scientific Reports
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