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https://www.readbyqxmd.com/read/28579578/the-t-box-transcription-factor-3-in-development-and-cancer
#1
Tarryn Willmer, Aretha Cooper, Jade Peres, Rehana Omar, Sharon Prince
T-box factors comprise an archaic family of evolutionary conserved transcription factors that regulate patterns of gene expression essential for embryonic development. The T-box transcription factor 3 (TBX3), a member of this family, is expressed in several tissues and plays critical roles in, among other structures, the heart, mammary gland and limbs and haploinsufficiency of the human TBX3 gene is the genetic basis for the autosomal dominant disorder, ulnar-mammary syndrome. Overexpression of TBX3 on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and a number of sarcoma subtypes...
June 4, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28553934/phenotypic-screening-identifies-axl-kinase-as-a-negative-regulator-of-an-alveolar-epithelial-cell-phenotype
#2
Naoya Fujino, Hiroshi Kubo, Rose A Maciewicz
Loss of epithelial barrier integrity is implicated in a number of human lung diseases. However, the molecular pathways underlying this process are poorly understood. In a phenotypic screen, we identified Axl kinase as a negative regulator of epithelial phenotype and function. Furthermore, suppression of Axl activity by a small molecule kinase inhibitor or downregulation of Axl expression by small interfering RNA led to: (1) the increase in epithelial surfactant protein expression; (2) a cell morphology transition from front-rear polarity to cuboidal shape; (3) the cytoskeletal re-organization resulting in decreased cell mobility; and (4) the acquisition of epithelial junctions...
May 29, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28521440/t-box-3-overexpression-is-associated-with-poor-prognosis-of-non-small-cell-lung-cancer
#3
Yueming Wu, Jiang Feng, Weiwei Hu, Yawei Zhang
T-box 3 (Tbx3), a member of the T-box transcription factor family, serves a crucial role in embryonic development and cancer progression. Previous studies have demonstrated the clinical significance of Tbx3 in numerous types of cancer. However, the expression level and pathological function of Tbx3 in non-small cell lung cancer (NSCLC) are unknown. To the best of our knowledge, the present study provided the first evidence demonstrating the clinicopathological significance of Tbx3 in NSCLC. Tbx3 was revealed to be overexpressed in NSCLC cell lines and tissues obtained from patients with NSCLC by reverse transcription-quantitative polymerase chain reaction and western blot analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28466692/dna-methylation-changes-in-tbx3-in-a-mouse-model-exposed-to-polybrominated-diphenyl-ethers
#4
Takashi Shimbo, June K Dunnick, Amy Brix, Deepak Mav, Ruchir Shah, John D Roberts, Paul A Wade
DE-71, a commercial mixture of polybrominated diphenyl ethers widely used in flame retardants, is a pervasive environmental contaminant due to its continuing release from waste material and its long half-life in humans. Although the genotoxic potential of DE-71 appears to be low based on bacterial mutagenicity, it remains a public health concern due to its reported involvement in tumor development. Molecular mechanisms by which DE-71 influences tumor incidence or progression remain understudied. We used liver carcinoma tissue from mice exposed to DE-71 to test the hypothesis that epigenetic alterations consistent with tumor development, specifically DNA methylation, result from long-term DE-71 exposure...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28432217/rar%C3%AE-2-is-required-for-vertebrate-somitogenesis
#5
Amanda Janesick, Weiyi Tang, Tuyen T L Nguyen, Bruce Blumberg
During vertebrate somitogenesis, retinoic acid is known to establish the position of the determination wavefront, controlling where new somites are permitted to form along the anteroposterior body axis. Less is understood about how RAR regulates somite patterning, rostral-caudal boundary setting, specialization of myotome subdivisions, or the specific RAR subtype that is required for somite patterning. Characterizing the function of RARβ has been challenging due to the absence of embryonic phenotypes in murine loss-of-function studies...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28392218/promyelocytic-leukemia-protein-is-an-essential-regulator-of-stem-cell-pluripotency-and-somatic-cell-reprogramming
#6
Christiana Hadjimichael, Konstantina Chanoumidou, Christoforos Nikolaou, Antonios Klonizakis, Gesthimani-Ioanna Theodosi, Takis Makatounakis, Joseph Papamatheakis, Androniki Kretsovali
Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28382491/tbx18-dependent-differentiation-of-brown-adipose-tissue-derived-stem-cells-toward-cardiac-pacemaker-cells
#7
Lei Chen, Zi-Jun Deng, Jian-Sheng Zhou, Rui-Juan Ji, Xi Zhang, Chuan-Sen Zhang, Yu-Quan Li, Xiang-Qun Yang
A cell-sourced biological pacemaker is a promising therapeutic approach for sick sinus syndrome (SSS) or severe atrial ventricular block (AVB). Adipose tissue-derived stem cells (ATSCs), which are optimal candidate cells for possible use in regenerative therapy for acute or chronic myocardial injury, have the potential to differentiate into spontaneous beating cardiomyocytes. However, the pacemaker characteristics of the beating cells need to be confirmed, and little is known about the underlying differential mechanism...
April 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28351298/aberrant-gene-specific-dna-methylation-signature-analysis-in-cervical-cancer
#8
Samatha Bhat, Shama Prasada Kabekkodu, Vinay Koshy Varghese, Sanjiban Chakrabarty, Sandeep P Mallya, Harish Rotti, Deeksha Pandey, Pralhad Kushtagi, Kapaettu Satyamoorthy
Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28298436/the-chromatin-remodeler-chd4-maintains-embryonic-stem-cell-identity-by-controlling-pluripotency-and-differentiation-associated-genes
#9
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28238063/functional-germline-variants-in-driver-genes-of-breast-cancer
#10
Stella Göhler, Miguel Inacio Da Silva Filho, Robert Johansson, Kerstin Enquist-Olsson, Roger Henriksson, Kari Hemminki, Per Lenner, Asta Försti
PURPOSE: Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. METHODS: After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs)...
April 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#11
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/28205312/essential-roles-of-tbx3-in-embryonic-skin-development-during-epidermal-stratification
#12
Ryo Ichijo, Yui Iizuka, Hirokazu Kubo, Fumiko Toyoshima
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function...
March 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28169326/novel-peptides-for-deciphering-structural-and-signalling-functions-of-e-cadherin-in-mouse-embryonic-stem-cells
#13
Joe M Segal, Christopher M Ward
We have previously shown that E-cadherin regulates the naive pluripotent state of mouse embryonic stem cells (mESCs) by enabling LIF-dependent STAT3 phosphorylation, with E-cadherin null mESCs exhibiting over 3000 gene transcript alterations and a switch to Activin/Nodal-dependent pluripotency. However, elucidation of the exact mechanisms associated with E-cadherin function in mESCs is compounded by the difficulty in delineating the structural and signalling functions of this protein. Here we show that mESCs treated with the E-cadherin neutralising antibody DECMA-1 or the E-cadherin binding peptide H-SWELYYPLRANL-NH2 (Epep) exhibit discrete profiles for pluripotent transcripts and NANOG protein expression, demonstrating that the type of E-cadherin inhibitor employed dictates the cellular phenotype of mESCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28145909/novel-tbx3-mutation-in-a-family-of-cypriot-ancestry-with-ulnar-mammary-syndrome
#14
George A Tanteles, Nayia Nicolaou, Andreas Syrimis, Rafaella Metaxa, Michael Nicolaou, Violetta Christophidou-Anastasiadou, Nicos Skordis
Ulnar-mammary syndrome (UMS) is an autosomal dominant disorder resulting from TBX3 haploinsufficiency. It typically affects limb, apocrine gland, hair, tooth and genital development and shows marked intrafamilial and interfamilial variability in phenotypic expression. We report a family (twin brothers and their father) affected with UMS because of a novel TBX3 mutation. The twin brothers showed classical features of UMS, whereas their father was mildly affected. The c.1423C>T (p.Q475*) nonsense mutation in exon 6 of the TBX3 gene identified in the patients by targeted Sanger sequencing is predicted to lead to premature termination of translation...
April 2017: Clinical Dysmorphology
https://www.readbyqxmd.com/read/28125717/epigenetic-alterations-affecting-transcription-factors-and-signaling-pathways-in-stromal-cells-of-endometriosis
#15
Iveta Yotova, Emily Hsu, Catherine Do, Aulona Gaba, Matthias Sczabolcs, Sabine Dekan, Lukas Kenner, Rene Wenzl, Benjamin Tycko
Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains...
2017: PloS One
https://www.readbyqxmd.com/read/28057270/the-roles-of-t-box-genes-in-vertebrate-limb-development
#16
REVIEW
C J Sheeba, M P O Logan
Members of the T-box gene family have diverse roles during embryogenesis and many play critical roles in the developing limb. This is exemplified by the fact that, in humans, mutations in T-box genes are associated with several congenital syndromes that include limb defects as part of their characteristic spectrum of abnormalities. T-box genes encode for evolutionary conserved transcription factors that include both transcriptional activators and repressors. The hallmark of T-box gene members is the presence of the eponymous DNA-binding T-box domain...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28057266/t-box-genes-in-the-kidney-and-urinary-tract
#17
REVIEW
A Kispert
T-box (Tbx) genes encode an ancient group of transcription factors that play important roles in patterning, specification, proliferation, and differentiation programs in vertebrate organogenesis. This is testified by severe organ malformation syndromes in mice homozygous for engineered null alleles of specific T-box genes and by the large number of human inherited organ-specific diseases that have been linked to mutations in these genes. One of the organ systems that has not been associated with loss of specific T-box gene function in human disease for long is the excretory system...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#18
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/27722056/life-threatening-cardiac-episode-in-a-polish-patient-carrying-contiguous-gene-microdeletion-of-the-tbx5-and-the-tbx3-genes
#19
Katarzyna Iwanicka-Pronicka, Magdalena Socha, Maria Jędrzejowska, Małgorzata Krajewska-Walasek, Aleksander Jamsheer
Holt-Oram syndrome (HOS) features radial ray hypoplasia, heart defect and cardiac conduction impairment. Ulnar-mammary syndrome (UMS) characterizes congenital defects of the ulnar side of the upper limbs, underdevelopment of apocrine glands including hypoplasia and the dysfunction of mammary glands, hypogonadism and obesity. Inheritance of both conditions is autosomal dominant, mutations or deletions are found in the TBX5 and TBX3 gene, respectively. The Polish patient presented short stature, obesity, congenital malformation of the radial and ulnar side of the upper limbs, heart block, hypogonadism and dysmorphic features...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27720610/tbx2-and-tbx3-act-downstream-of-shh-to-maintain-canonical-wnt-signaling-during-branching-morphogenesis-of-the-murine-lung
#20
Timo H Lüdtke, Carsten Rudat, Irina Wojahn, Anna-Carina Weiss, Marc-Jens Kleppa, Jennifer Kurz, Henner F Farin, Anne Moon, Vincent M Christoffels, Andreas Kispert
Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 act together in the lung mesenchyme to maintain branching morphogenesis. Expression of both genes depends on epithelially derived Shh signaling, with additional modulation by Bmp, Wnt, and Tgfβ signaling...
October 24, 2016: Developmental Cell
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