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https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#1
Ken J Kron, Alexander Murison, Stanley Zhou, Vincent Huang, Takafumi N Yamaguchi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Mathieu Lupien
TMPRSS2-ERG (T2E) structural rearrangements typify ∼50% of prostate tumors and result in overexpression of the ERG transcription factor. Using chromatin, genomic and expression data, we show distinct cis-regulatory landscapes between T2E-positive and non-T2E primary prostate tumors, which include clusters of regulatory elements (COREs). This difference is mediated by ERG co-option of HOXB13 and FOXA1, implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression...
August 7, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28767682/genetic-variability-and-functional-implication-of-the-long-control-region-in-hpv-16-variants-in-southwest-china
#2
Juemin Xi, Junying Chen, Miaoling Xu, Hongying Yang, Jia Luo, Yue Pan, Xiaodan Wang, Lijuan Qiu, Jiajia Yang, Qiangming Sun
HPV-16 long control region (LCR) has been shown to be the most variable region of the HPV-16 genome and may play important roles in viral persistence and the development of cervical cancer. This study aimed to assess the risk of HPV-16 LCR variants for cervical cancer in women of Southwest China. 2146 cervical scrapings of volunteer outpatients and 74 cervical cancer tissues were screened.14 entire HPV-16 LCRs from asymptomatic carriers and 34 entire HPV-16 LCRs from cervical cancer patients were successfully amplified and sequenced to align to others described...
2017: PloS One
https://www.readbyqxmd.com/read/28757253/enhancer-reprogramming-promotes-pancreatic-cancer-metastasis
#3
Jae-Seok Roe, Chang-Il Hwang, Tim D D Somerville, Joseph P Milazzo, Eun Jung Lee, Brandon Da Silva, Laura Maiorino, Hervé Tiriac, C Megan Young, Koji Miyabayashi, Dea Filippini, Brianna Creighton, Richard A Burkhart, Jonathan M Buscaglia, Edward J Kim, Jean L Grem, Audrey J Lazenby, James A Grunkemeyer, Michael A Hollingsworth, Paul M Grandgenett, Mikala Egeblad, Youngkyu Park, David A Tuveson, Christopher R Vakoc
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo...
July 25, 2017: Cell
https://www.readbyqxmd.com/read/28757167/chemical-cocktails-enable-hepatic-reprogramming-of-mouse-fibroblasts-with-a-single-transcription-factor
#4
Ren Guo, Wei Tang, Qianting Yuan, Lijian Hui, Xin Wang, Xin Xie
Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28756535/foxa1-hypermethylation-link-between-parity-and-er-negative-breast-cancer-in-african-american-women
#5
Allyson C Espinal, Matthew F Buas, Dan Wang, David Ting-Yuan Cheng, Lara Sucheston-Campbell, Qiang Hu, Li Yan, Rochelle Payne-Ondracek, Eduardo Cortes, Li Tang, Zhihong Gong, Gary Zirpoli, Thaer Khoury, Song Yao, Angela Omilian, Kitaw Demissie, Elisa V Bandera, Song Liu, Christine B Ambrosone, Michael J Higgins
BACKGROUND: Reproductive factors, particularly parity, have differential effects on breast cancer risk according to estrogen receptor (ER) status, especially among African American (AA) women. One mechanism could be through DNA methylation, leading to altered expression levels of genes important in cell fate decisions. METHODS: Using the Illumina 450K BeadChip, we compared DNA methylation levels in paraffin-archived tumor samples from 383 AA and 350 European American (EA) women in the Women's Circle of Health Study (WCHS)...
July 29, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28732322/effects-of-environmental-pollutants-on-signaling-pathways-in-rat-pituitary-gh3-adenoma-cells
#6
Nicoletta Fortunati, Federica Guaraldi, Valentina Zunino, Federica Penner, Valentina D'Angelo, Francesco Zenga, Francesca Pecori Giraldi, Maria Graziella Catalano, Emanuela Arvat
An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH-secreting pituitary adenomas. Based on these premises, the aim of the study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells...
July 18, 2017: Environmental Research
https://www.readbyqxmd.com/read/28721490/foxa1-and-ck14-as-markers-of-luminal-and-basal-subtypes-in-histologic-variants-of-bladder-cancer-and-their-associated-conventional-urothelial-carcinoma
#7
Joshua I Warrick, Matthew Kaag, Jay D Raman, Wilson Chan, Truc Tran, Sudhir Kunchala, Lauren Shuman, David DeGraff, Guoli Chen
Invasive bladder cancer is diverse, and includes several named histomorphologies that differ from conventional urothelial carcinoma, termed "histologic variants." By transcriptional analysis, bladder cancers can be divided into luminal and basal subtypes. In this paper, we study associations between markers of transcriptional subtypes and variant histology in a retrospective cohort of 309 cystectomy specimens. Histology slides were methodically reviewed for all cases, and variant histology was documented. Immunohistochemistry for FOXA1 (luminal marker) and CK14 (basal maker) was performed on histologic variants and their associated conventional urothelial carcinomas...
July 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28700586/systematic-identification-and-characterization-of-regulatory-elements-derived-from-human-endogenous-retroviruses
#8
Jumpei Ito, Ryota Sugimoto, Hirofumi Nakaoka, Shiro Yamada, Tetsuaki Kimura, Takahide Hayano, Ituro Inoue
Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs)...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28673244/a-comprehensive-genomic-pan-cancer-classification-using-the-cancer-genome-atlas-gene-expression-data
#9
Yuanyuan Li, Kai Kang, Juno M Krahn, Nicole Croutwater, Kevin Lee, David M Umbach, Leping Li
BACKGROUND: The Cancer Genome Atlas (TCGA) has generated comprehensive molecular profiles. We aim to identify a set of genes whose expression patterns can distinguish diverse tumor types. Those features may serve as biomarkers for tumor diagnosis and drug development. METHODS: Using RNA-seq expression data, we undertook a pan-cancer classification of 9,096 TCGA tumor samples representing 31 tumor types. We randomly assigned 75% of samples into training and 25% into testing, proportionally allocating samples from each tumor type...
July 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28662305/degranulation-and-shrinkage-of-dark-cells-in-eccrine-glands-and-elevated-serum-carcinoembryonic-antigen-in-patients-with-acquired-idiopathic-generalized-anhidrosis
#10
K Sano, M Asahina, T Uehara, K Matsumoto, N Araki, R Okuyama
BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion of which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). OBJECTIVE: Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA...
June 29, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28659719/somatic-mutation-analyses-in-studies-of-the-clonal-evolution-and-diagnostic-targets-of-prostate-cancer
#11
REVIEW
Dmitry S Mikhaylenko, Gennady D Efremov, Vladimir V Strelnikov, Dmitry V Zaletaev, Boris Y Alekseev
Prostate cancer (PC) is the most common uro-oncological disease in the global population and still requires a more efficient laboratory diagnosis. Point mutations of oncogenes and tumor sup-pressor genes are the most frequent molecular genetic events in carcinogenesis. The mutations are re-sponsible, to a great extent, for the clonal evolution of cancer and can be considered as primary candi-date molecular markers of PC. Using next-generation sequencing to analyze the mutations in PC, the main molecular PC subtypes were identified, which depended on the presence of fusion genes and FOXA1, CHD1, and SPOP point mutations; other driver mutations responsible for the progression of PC subclones were also characterized...
June 2017: Current Genomics
https://www.readbyqxmd.com/read/28658208/recurrent-and-functional-regulatory-mutations-in-breast-cancer
#12
Esther Rheinbay, Prasanna Parasuraman, Jonna Grimsby, Grace Tiao, Jesse M Engreitz, Jaegil Kim, Michael S Lawrence, Amaro Taylor-Weiner, Sergio Rodriguez-Cuevas, Mara Rosenberg, Julian Hess, Chip Stewart, Yosef E Maruvka, Petar Stojanov, Maria L Cortes, Sara Seepo, Carrie Cibulskis, Adam Tracy, Trevor J Pugh, Jesse Lee, Zongli Zheng, Leif W Ellisen, A John Iafrate, Jesse S Boehm, Stacey B Gabriel, Matthew Meyerson, Todd R Golub, Jose Baselga, Alfredo Hidalgo-Miranda, Toshi Shioda, Andre Bernards, Eric S Lander, Gad Getz
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28632777/immunohistochemiocal-subtyping-using-ck20-and-ck5-can-identify-urothelial-carcinomas-of-the-upper-urinary-tract-with-a-poor-prognosis
#13
Danijel Sikic, Bastian Keck, Sven Wach, Helge Taubert, Bernd Wullich, Peter J Goebell, Andreas Kahlmeyer, Peter Olbert, Philipp Isfort, Wilhelm Nimphius, Arndt Hartmann, Johannes Giedl
PURPOSE: Genome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND METHODS: Tumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1)...
2017: PloS One
https://www.readbyqxmd.com/read/28608964/hbx-elevated-msl2-modulates-hbv-cccdna-through-inducing-degradation-of-apobec3b-to-enhance-hepatocarcinogenesis
#14
Yuen Gao, Jinyan Feng, Guang Yang, Shuqin Zhang, Yunxia Liu, Yanan Bu, Mingming Sun, Man Zhao, Fuquan Chen, Weiying Zhang, Lihong Ye, Xiaodong Zhang
Chronic hepatitis B virus (HBV) infection is a leading cause in the occurrence of hepatitis B, liver cirrhosis and liver cancer, in which nuclear HBV covalently closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence, plays crucial roles. In the present study, we explored the hypothesis that HBV X protein (HBx)-elevated male-specific lethal 2 (MSL2) activated HBV replication via modulating cccDNA in hepatoma cells, leading to hepatocarcinogenesis. Immunohistochemical analysis revealed that the expression of MSL2 was positively associated with that of HBV and was increased in the liver tissues of HBV-transgenic mice and clinical HCC patients...
June 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28565816/microrna-212-targets-foxa1-and-suppresses-the-proliferation-and-invasion-of-intrahepatic-cholangiocarcinoma-cells
#15
Lei Zhu, Feizhou Huang, Gang Deng, Wanpin Nie, Wei Huang, Hongbo Xu, Shaopeng Zheng, Zhongjie Yi, Tao Wan
[This retracts the article DOI: 10.3892/etm.2016.3824.].
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28546130/a-study-of-foxa1-expression-in-thyroid-tumors
#16
Daisuke Nonaka
FoxA1 regulates a variety of tissues during embryogenesis and early life. In thyroid, FoxA1 expression has recently been shown in C cells and medullary thyroid carcinomas but not in follicular cells. FoxA1 has also been proposed as potential oncogene in anaplastic thyroid carcinomas. However, FoxA1 expression has not been extensively investigated in a spectrum of thyroid non-neoplastic lesions and tumors. A variety of thyroid tumors and lesions and their morphologic mimics were stained with monoclonal anti-FoxA1 antibody...
May 22, 2017: Human Pathology
https://www.readbyqxmd.com/read/28534958/mir-204-regulates-the-biological-behavior-of-breast-cancer-mcf-7-cells-by-directly-targeting-foxa1
#17
Si-Qiao Shen, Lan-Shan Huang, Xiao-Ling Xiao, Xiao-Fei Zhu, Dan-Dan Xiong, Xue-Mei Cao, Kang-Lai Wei, Gang Chen, Zhen-Bo Feng
MicroRNAs (miRNAs) are short, non-protein-coding RNAs and transcripts that are 18-24 nt in length. miR-204 was first identified as an anti-oncogene and is reported to be downregulated in non-small cell lung cancer, glioma, gastric and thyroid cancer. Recent studies have proposed that a low level of miR-204 expression is associated with tumor progression and disease outcome in breast cancer. Forkhead box A1 (FOXA1), a transcription factor, plays a crucial role in breast cancer and has been predicted as a target of miR-204...
May 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28530243/corrigendum-neuronal-ifn-beta-induced-pi3k-akt-foxa1-signalling-is-essential-for-generation-of-foxa1-treg-cells
#18
Yawei Liu, Andrea Marin, Patrick Ejlerskov, Louise Munk Rasmussen, Marco Prinz, Shohreh Issazadeh-Navikas
This corrects the article DOI: 10.1038/ncomms14709.
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28514748/a-transcriptional-complex-composed-of-er-%C3%AE-gata3-foxa1-and-ell3-regulates-il-20-expression-in-breast-cancer-cells
#19
Jae Yong Lee, Young Joon Park, Nuri Oh, Kyu Bum Kwack, Kyung-Soon Park
Interleukin-20 (IL-20) is a member of the IL-10 family. IL-20 expression is regulated by a transcription elongation factor, Ell3, in estrogen receptor-positive (ER(+)) breast cancer cells. In this study, we demonstrated that ER(α), GATA3 and FOXA1 form a transcriptional complex with Ell3 to regulate IL-20 expression in ER(+) breast cancer cells. We also determined that GATA3 and FOXA1 share a binding site with ER(α) in the interleukin-20 promoter. Furthermore, we found that FOXA1 represses IL-20 expression, whereas GATA3 and ER(α) activate it...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488543/the-transcription-factor-foxa1-induces-epithelial-ovarian-cancer-tumorigenesis-and-progression
#20
Li-Li Wang, Yin-Ling Xiu, Xi Chen, Kai-Xuan Sun, Shuo Chen, Dan-Dan Wu, Bo-Liang Liu, Yang Zhao
FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily, plays an important role in tumor occurrence and development. However, the relationship between FOXA1 and ovarian cancer has not been reported. We examined normal ovarian tissue and ovarian cancer tissue and found increased FOXA1 expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays demonstrated that transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian cancer cell lines decreased cell proliferation and induced apoptosis and S-phase arrest...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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