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https://www.readbyqxmd.com/read/28938408/pioneer-factors-foxa1-and-foxa2-assist-selective-glucocorticoid-receptor-signaling-in-human-endometrial-cells
#1
Shannon Whirledge, Edwina P Kisanga, Robert N Taylor, John A Cidlowski
Successful pregnancy relies on dynamic control of cell signaling in order to achieve uterine receptivity and the necessary biological changes required for endometrial decidualization, embryo implantation, and fetal development. Glucocorticoids are master regulators of intracellular signaling and can directly regulate embryo implantation and endometrial remodeling during murine pregnancy. In immortalized human uterine cells, we have shown that glucocorticoids and estradiol co-regulate thousands of genes. Recently, glucocorticoids and estradiol were shown to co-regulate the expression of Left-right determination factor 1 (LEFTY1), previously implicated in the regulation of decidualization...
August 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938404/the-transcriptome-of-estrogen-independent-mammary-growth-in-female-mice-reveals-that-not-all-mammary-glands-are-created-equally
#2
Grace E Berryhill, Danielle G Lemay, Josephine F Trott, Lucila Aimo, Adam L Lock, Russell C Hovey
Allometric growth of ducts in the mammary glands (MG) is widely-held to be estrogen (E)-dependent. We previously discovered that the dietary fatty acid trans-10, cis-12 conjugated linoleic acid (CLA) stimulates E-independent allometric growth and TEB formation in ovariectomized mice. Given the similar phenotype induced by E and CLA, we investigated the shared and/or divergent mechanisms underlying these changes. We confirmed MG growth induced by CLA is temporally distinct from that elicited by E, then used RNA-Sequencing to compare the transcriptome of the MG during similar proliferative and morphological states...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28927002/predicting-variation-of-dna-shape-preferences-in-protein-dna-interaction-in-cancer-cells-with-a-new-biophysical-model
#3
Kirill Batmanov, Junbai Wang
DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#4
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#5
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28918284/new-insights-into-human-female-reproductive-tract-development
#6
Stanley J Robboy, Takeshi Kurita, Laurence Baskin, Gerald R Cunha
We present a detailed review of the embryonic and fetal development of the human female reproductive tract utilizing specimens from the 5th through the 22nd gestational week. Hematoxylin and eosin (H&E) as well as immunohistochemical stains were used to study the development of the human uterine tube, endometrium, myometrium, uterine cervix and vagina. Our study revisits and updates the classical reports of Koff (1933) and Bulmer (1957) and presents new data on development of human vaginal epithelium. Koff proposed that the upper 4/5ths of the vagina is derived from Müllerian epithelium and the lower 1/5th derived from urogenital sinus epithelium, while Bulmer proposed that vaginal epithelium derives solely from urogenital sinus epithelium...
August 11, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28884749/comprehensive-clinical-and-molecular-analyses-of-neuroendocrine-carcinomas-of-the-breast
#7
Marion Lavigne, Emmanuelle Menet, Jean-Christophe Tille, Marick Lae, Laetitia Fuhrmann, Claire Bonneau, Gabrielle Deniziaut, Samia Melaabi, Charlotte C K Ng, Caterina Marchiò, Roman Rouzier, Ivan Bièche, Anne Vincent-Salomon
Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial in the literature. The 2012 WHO classification of breast cancer categorizes neuroendocrine carcinomas into three morphologically distinct subtypes: well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. We aimed to gain insight into the clinical, morphologic, phenotypic, and molecular features of 47 neuroendocrine breast carcinomas...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28867731/foxa1-induces-e-cadherin-expression-at-the-protein-level-via-suppression-of-slug-in-epithelial-breast-cancer-cells
#8
Erina Anzai, Kensuke Hirata, Misato Shibazaki, Chiaki Yamada, Mariko Morii, Takuya Honda, Naoto Yamaguchi, Noritaka Yamaguchi
Epithelial-to-mesenchymal transition (EMT) is an important process during embryonic development and tumor progression by which adherent epithelial cells acquire mesenchymal properties. Forkhead box protein A1 (FOXA1) is a transcriptional regulator preferentially expressed in epithelial breast cancer cells, and its expression is lost in mesenchymal breast cancer cells. However, the implication of this biased expression of FOXA1 in breast cancer is not fully understood. In this study, we analyzed the involvement of FOXA1 in EMT progression in breast cancer, and found that stable expression of FOXA1 in the mesenchymal breast cancer MDA-MB-231 cells strongly induced the epithelial marker E-cadherin at the mRNA and protein levels...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28865492/pathobiology-of-the-129-stat1-mouse-model-of-human-age-related-er-positive-breast-cancer-with-an-immune-infiltrate-excluded-phenotype
#9
Hidetoshi Mori, Jane Q Chen, Robert D Cardiff, Zsófia Pénzváltó, Neil E Hubbard, Louis Schuetter, Russell C Hovey, Josephine F Trott, Alexander D Borowsky
BACKGROUND: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 (tm1Rds)) develop estrogen receptor-positive (ER(+)), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points. In addition, we investigate tumor progression in the 129:Stat1 (-/-) host compared with wild-type 129/SvEv, and we describe the immune cell reaction to the tumors...
September 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28855426/neural-differentiation-of-fibroblasts-induced-by-intracellular-co-delivery-of-ascl1-brn2-and-foxa1-via-a-non-viral-vector-of-cationic-polysaccharide
#10
Qingtong Yu, Jingjing Chen, Wenwen Deng, Xia Cao, Michael Adu-Frimpong, Jiangnan Yu, Xi-Ming Xu
Direct reprogramming of other somatic cells into neurons is an alternative strategy for the recovery of injured nervous system. In this work we developed a new non-viral gene carrier based on Porphyra yezoensis polysaccharide (PYP). After modification with ethylenediamine, the cationized Porphyra yezoensis polysaccharide (Ed-PYP) was combined with plasmids encoding Ascl1, Brn2 and FoxA1 to form spherical nanoscale particles (Ed-PYP-pABF nanoparticles). Cytotoxicity assay proved that Ed-PYP-pABF nanoparticles had a safer property than Lipofectamine2000 and polyetherimide (PEI)...
August 31, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28844448/spatiotemporal-expression-of-foxa1-correlates-with-reactive-gliosis-after-spinal-cord-injury
#11
Dongliang Wang, Siqing Wang, Biao Ji, Minqian Zheng
Forkhead box A1 (FOXA1) is a member of the FOX family of transcription factors and involved in various mammalian processes. However, the expression and function of FOXA1 in central nervous system (CNS) are still with limited acquaintance. In present study, we performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of FOXA1 expression in spinal cord. We found that FOXA1 protein levels were significantly increased after SCI and we observed that the expression of FOXA1 is enhanced in the white matter...
August 18, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28843920/tumour-infiltrating-lymphocytes-are-predictors-of-lymph-node-metastasis-in-early-gastric-cancers
#12
Joo Young Kim, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Yang-Seok Chae
Lymph node metastasis (LNM) is an important factor for predicting prognosis and selecting appropriate treatment in early gastric cancers (EGCs). We investigated the histopathological and microenvironmental predictors of LNM in EGCs. We retrieved 43 cases of EGC without LNM and 59 cases with LNM. Clinicopathological variables and tumour-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction (CLR), tumour stromal percentage (TSP), and FOXA1 expression were evaluated and correlated with LNM. Among the 102 cases, 68 cases (66...
October 2017: Pathology
https://www.readbyqxmd.com/read/28842510/impact-of-therapy-on-genomics-and-transcriptomics-in-high-risk-prostate-cancer-treated-with-neoadjuvant-docetaxel-and-androgen-deprivation-therapy
#13
Himisha Beltran, Alexander W Wyatt, Edmund Chedgy, Adam Donoghue, Matti Annala, Evan Warner, Kevin Beja, Michael Sigouros, Fan Mo, Ladan Fazli, Colin C Collins, James A Eastham, Michael J Morris, Mary-Ellen Taplin, Andrea Sboner, Susan Halabi, Martin E Gleave
BACKGROUND: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. METHODS: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center...
August 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28841414/reprogramming-enhancers-to-drive-metastasis
#14
COMMENT
Raul Mostoslavsky, Nabeel Bardeesy
Acquired molecular changes can promote the spreading of primary tumor cells to distant tissues. In this issue of Cell, Roe et al. show that metastatic progression of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcriptional program specifying early endodermal stem cells.
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28816236/microrna-132-suppresses-cell-proliferation-in-human-breast-cancer-by-directly-targeting-foxa1
#15
Dan Wang, Jin Ren, Hui Ren, Jin-Ling Fu, Dan Yu
Dysregulation of microRNAs (miRNAs) has been implicated in cancer. Recently, miR-132 has been reported to be downregulated in the tissues of patients with breast cancer. In this study, we investigated the functional role of miR-132 and its direct target FOXA1 in breast cancer cells. In 30 human breast cancer tissues, FOXA1 was significantly overexpressed and negatively correlated with miR-132 expression. A bioinformatics analysis suggested that FOXA1 was a potential target of miR-132. Furthermore, dual luciferase reporter assays revealed that miR-132 dose-dependently inhibited the luciferase activity of the wt 3'UTR of FOXA1 rather than the mut 3'UTR of FOXA1 in human MDA-MB-468 and SK-BR3 breast cancer cells...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#16
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...
September 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
#17
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
#18
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...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28757167/chemical-cocktails-enable-hepatic-reprogramming-of-mouse-fibroblasts-with-a-single-transcription-factor
#19
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
#20
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
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