Abstract:
:CDH3/P-cadherin is a classical cadherin. Overexpression of which has been associated with proliferative lesions of high histological grade, decreased cell polarity and poor survival of patients with breast cancer. In vitro studies showed that it can be up-regulated by ICI 182,780, suggesting that the lack of ERalpha signalling is responsible for the aberrant P-cadherin overexpression and for its role in inducing breast cancer cell invasion and migration. However, the mechanism by which ER-signalling inhibition leads to P-cadherin expression is still unknown. The aim of this study was to explore the molecular mechanism linking the ERalpha-signalling and P-cadherin-regulated expression in breast cancer cell lines. This study showed that ICI 182,780 is able to increase CDH3 promoter activity, inducing high levels of the active chromatin mark H3 lysine 4 dimethylation. We also observed, for the first time, that the transcription factor C/EBPbeta is able to up-regulate CDH3 promoter activity in breast cancer cells. Moreover, we showed that the expression of P-cadherin and C/EBPbeta are highly associated in human breast carcinomas and linked with a worse prognosis of breast cancer patients. This study demonstrates the existence of an epigenetic regulation by which ICI 182,780 up-regulates P-cadherin expression in MCF-7/AZ breast cancer cells through chromatin remodelling at CDH3 promoter, bringing forward the growing evidence that ERalpha signalling-abrogation by anti-oestrogens is able to induce the expression of ERalpha-repressed genes which, in the appropriate cell biology context, may contribute to a breast cancer cell invasion phenotype.CDH3 GenBank accession no. NT_010498.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Albergaria A,Ribeiro AS,Pinho S,Milanezi F,Carneiro V,Sousa B,Sousa S,Oliveira C,Machado JC,Seruca R,Paredes J,Schmitt Fdoi
10.1093/hmg/ddq134subject
Has Abstractpub_date
2010-07-01 00:00:00pages
2554-66issue
13eissn
0964-6906issn
1460-2083pii
ddq134journal_volume
19pub_type
杂志文章abstract::The clinical manifestations of inherited neurodegenerative diseases are often delayed for periods from years to decades. This observation has led to the idea that, in these disorders, neurons die from cumulative damage. A critical prediction of the cumulative damage hypothesis is that the probability of neuronal death...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/10.20.2269
更新日期:2001-10-01 00:00:00
abstract::X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr536
更新日期:2012-03-01 00:00:00
abstract::Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is caused by multiple genetic and environmental factors. The clinical and immunological features of GD and HT are distinct; however, there are multiplex families with both GD and HT, and cases in which GD evolves into H...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.13.1379
更新日期:2001-06-15 00:00:00
abstract::Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa077
更新日期:2020-06-03 00:00:00
abstract::To determine factors governing triplet repeat expansion at FMR1, we need to understand the basis of normal variation. We have sequenced the FMR1 repeat from 102 normal X chromosomes and show that most are interrupted with a regularly spaced AGG trinucleotide giving an ordered structure to the array. Five types of arra...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.9.1553
更新日期:1994-09-01 00:00:00
abstract::Selenoprotein N (SelN) deficiency causes a group of inherited neuromuscular disorders termed SEPN1-related myopathies (SEPN1-RM). Although the function of SelN remains unknown, recent data demonstrated that it is dispensable for mouse embryogenesis and suggested its involvement in the regulation of ryanodine receptors...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq515
更新日期:2011-02-15 00:00:00
abstract::Nineteen Wnt ligands and 10 Frizzled (Fz) receptors mediate multiple distinct cellular events during neuronal development. However, their precise roles in cell-type specification and organogenesis are poorly delineated because of overlapping functions and expression profiles. Here, we have explored the role of two clo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr616
更新日期:2012-04-15 00:00:00
abstract::Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed a limited therapeutic time window and systemic aspects of the disease. This raises a fundamental question of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa146
更新日期:2020-09-29 00:00:00
abstract::KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr399
更新日期:2011-12-01 00:00:00
abstract::Familial tumoral calcinosis (FTC) is an autosomal recessive disorder characterized by ectopic calcifications and elevated serum phosphate levels. Recently, mutations in the GALNT3 gene have been described to cause FTC. The FTC phenotype is regarded as the metabolic mirror image of hypophosphatemic conditions, where ca...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi034
更新日期:2005-02-01 00:00:00
abstract::Extracellular deposition of amyloid-beta (Aβ) peptide, a metabolite of sequential cleavage of amyloid precursor protein (APP), is a critical step in the pathogenesis of Alzheimer's disease (AD). While death-associated protein kinase 1 (DAPK1) is highly expressed in AD brains and its genetic variants are linked to AD r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw114
更新日期:2016-06-15 00:00:00
abstract::Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in si...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.18.2175
更新日期:2002-09-01 00:00:00
abstract::We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorphisms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome region...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.17.1987
更新日期:2002-08-15 00:00:00
abstract::Degradation of fibrillar collagens is believed to be involved in the rupture of the fetal membranes during normal parturition and when the membranes rupture prematurely. Matrix metalloproteinase 1 (MMP1) is a key enzyme involved in extracellular matrix turnover, and genetic variation in the MMP1 promoter is associated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm381
更新日期:2008-04-15 00:00:00
abstract::Lipocalins are carrier proteins for hydrophobic molecules in many biological fluids. In the oral sphere (nasal mucus, saliva, tears), they have an environmental biosensor function and are involved in the detection of odours and pheromones. Herein, we report the first identification of human lipocalins involved in odor...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.2.289
更新日期:2000-01-22 00:00:00
abstract::We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear backgr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm045
更新日期:2007-04-15 00:00:00
abstract::Obesity is a major public health problem with strong genetic determination; however, the genetic factors underlying obesity are largely unknown. In this study, we performed a genome-wide association scan for obesity by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000 unrelated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn072
更新日期:2008-06-15 00:00:00
abstract::To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.6.387
更新日期:1992-09-01 00:00:00
abstract::Manipulation of the mouse genome by site-specific mutagenesis has been extensively used to study gene function and model human disorders. Mouse models of myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene, have been generated by homologous recombinatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt038
更新日期:2013-05-01 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chines...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw346
更新日期:2016-12-15 00:00:00
abstract::Newborn screening (NBS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) revealed a higher birth prevalence and genotypic variability than previously estimated, including numerous novel missense mutations in the ACADM gene. On average, these mutations are associated with milder biochemical phenotypes raising...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp079
更新日期:2009-05-01 00:00:00
abstract::A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm136
更新日期:2007-10-15 00:00:00
abstract::Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr593
更新日期:2012-04-01 00:00:00
abstract::Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone (or dihydrotestost...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu419
更新日期:2015-01-01 00:00:00
abstract::Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked My...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.5.821
更新日期:2000-03-22 00:00:00
abstract::Although considered the most common heritable cause of neurodevelopmental disability, precise prevalence figures for the FMR1 mutation in the general population are lacking. Since no fragile X premutation alleles have yet been observed to originate from FMR1 alleles within the normal size range, there is also little i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.3.393
更新日期:1994-03-01 00:00:00
abstract::Lafora progressive myoclonus epilepsy, caused by defective laforin or malin, insidiously present in normal teenagers with cognitive decline, followed by rapidly intractable epilepsy, dementia and death. Pathology reveals neurodegeneration with neurofibrillary tangle formation and Lafora bodies (LBs). LBs are deposits ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi306
更新日期:2005-09-15 00:00:00
abstract::Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz056
更新日期:2019-07-01 00:00:00
abstract::The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, wer...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.12.2033
更新日期:1996-12-01 00:00:00