JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI.

Abstract:

INTRODUCTION:Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression through transcriptional repression of the tumor suppressor aplasia Ras homolog member I (ARHI). METHODS:Immunohistochemistry was performed to examine protein expressions in 155 cases of breast cancer and 30 non-neoplastic tissues. Spearman correlation analysis was used to analyze the correlation between JMJD2A expression and clinical parameters as well as several tumor regulators in 155 cases of breast cancer. Gene and protein expressions were monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Results from knockdown of JMJD2A, overexpression of JMJD2A, Co-immunoprecipitation (Co-IP) assay, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) elucidated molecular mechanisms of JMJD2A action in breast cancer progression. Furthermore, the effects of ARHI overexpression on JMJD2A-mediated tumor progression were investigated in vitro and in vivo. For in vitro experiments, cell proliferation, wound-healing, migration and invasion were monitored by cell counting, scratch and Boyden Chamber assays. For in vivo experiments, control cells and cells stably expressing JMJD2A alone or together with ARHI were inoculated into mammary fat pads of mice. Tumor volume, tumor weight and metastatic nodules were measured by caliper, electronic balance and nodule counting, respectively. RESULTS:JMJD2A was highly expressed in human breast cancers and positively correlated with tumor progression. Knockdown of JMJD2A increased ARHI expression whereas overexpression of JMJD2A decreased ARHI expression at both protein and mRNA levels. Furthermore, E2Fs and histone deacetylases were involved in the transcriptional repression of ARHI expression by JMJD2A. And the aggressive behavior of JMJD2A in breast cancers could be reversed by re-expression of ARHI in vitro and in vivo. CONCLUSION:We demonstrated a cancer-promoting effect of JMJD2A and defined a novel molecular pathway contributing to JMJD2A-mediated breast cancer progression.

journal_name

Breast Cancer Res

authors

Li LL,Xue AM,Li BX,Shen YW,Li YH,Luo CL,Zhang MC,Jiang JQ,Xu ZD,Xie JH,Zhao ZQ

doi

10.1186/bcr3667

subject

Has Abstract

pub_date

2014-05-30 00:00:00

pages

R56

issue

3

eissn

1465-5411

issn

1465-542X

pii

bcr3667

journal_volume

16

pub_type

杂志文章
  • Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis!

    abstract::The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critica...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr1653

    authors: Anderson SM,Rudolph MC,McManaman JL,Neville MC

    更新日期:2007-01-01 00:00:00

  • Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival.

    abstract:INTRODUCTION:Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases an...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1636

    authors: Fulford LG,Reis-Filho JS,Ryder K,Jones C,Gillett CE,Hanby A,Easton D,Lakhani SR

    更新日期:2007-01-01 00:00:00

  • Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients.

    abstract:BACKGROUND:Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and r...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-017-0916-4

    authors: Helland T,Henne N,Bifulco E,Naume B,Borgen E,Kristensen VN,Kvaløy JT,Lash TL,Alnæs GIG,van Schaik RH,Janssen EAM,Hustad S,Lien EA,Mellgren G,Søiland H

    更新日期:2017-11-28 00:00:00

  • Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study.

    abstract:INTRODUCTION:Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer. METHODS:We evaluated the contribution of germline mutations in the DD...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1668

    authors: Broeks A,Braaf LM,Huseinovic A,Nooijen A,Urbanus J,Hogervorst FB,Schmidt MK,Klijn JG,Russell NS,Van Leeuwen FE,Van 't Veer LJ

    更新日期:2007-01-01 00:00:00

  • GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells.

    abstract:INTRODUCTION:Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be invo...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1617

    authors: Abba MC,Nunez MI,Colussi AG,Croce MV,Segal-Eiras A,Aldaz CM

    更新日期:2006-01-01 00:00:00

  • Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members.

    abstract::ErbB (also termed HER) receptors are expressed in various tissues of epithelial, mesenchymal and neuronal origin, in which they are involved in the control of diverse biological processes such as proliferation, differentiation, migration and apoptosis. Furthermore, their deregulated expression has been implicated in m...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr327

    authors: Olayioye MA

    更新日期:2001-01-01 00:00:00

  • Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells.

    abstract:INTRODUCTION:Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay b...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr3580

    authors: Hugo HJ,Pereira L,Suryadinata R,Drabsch Y,Gonda TJ,Gunasinghe NP,Pinto C,Soo ET,van Denderen BJ,Hill P,Ramsay RG,Sarcevic B,Newgreen DF,Thompson EW

    更新日期:2013-11-27 00:00:00

  • Familial risks of breast cancer.

    abstract::A recent analysis by the Collaborative Group on Hormonal Factors in Breast Cancer has provided the most precise quantification to date of the familial risks of breast cancer. The familial relative risks are shown to decrease from more than fivefold in women younger than age 40 years with a first-degree relative aged y...

    journal_title:Breast cancer research : BCR

    pub_type: 社论

    doi:10.1186/bcr448

    authors: Easton DF

    更新日期:2002-01-01 00:00:00

  • Initiating breast cancer by PIK3CA mutation.

    abstract::PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr3103

    authors: Miller TW

    更新日期:2012-02-07 00:00:00

  • Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer.

    abstract:INTRODUCTION:The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer. METHODS:We screened...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr3182

    authors: Wu X,Zhu Z,Li W,Fu X,Su D,Fu L,Zhang Z,Luo A,Sun X,Fu L,Dong JT

    更新日期:2012-05-08 00:00:00

  • Anti-VEGF therapy as adjuvant therapy: clouds on the horizon?

    abstract::Anti-angiogenic therapies have demonstrated their value in the setting of advanced cancer, and are being explored for use in micrometastatic disease. Recent preclinical studies suggest that adjuvant anti-vascular endothelial growth factor (VEGF) therapies may increase the risk of metastasis. How concerning are these p...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2250

    authors: Schneider BP,Sledge GW Jr

    更新日期:2009-01-01 00:00:00

  • A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGFβ signaling in the mammary gland.

    abstract:INTRODUCTION:Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference (RNAi)-based knockdown approaches to fully a...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2728

    authors: Kohn EA,Du Z,Sato M,Van Schyndle CM,Welsh MA,Yang YA,Stuelten CH,Tang B,Ju W,Bottinger EP,Wakefield LM

    更新日期:2010-01-01 00:00:00

  • Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer.

    abstract:BACKGROUND:The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast cancer pat...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-019-1127-y

    authors: Kennedy SP,Han JZR,Portman N,Nobis M,Hastings JF,Murphy KJ,Latham SL,Cadell AL,Miladinovic D,Marriott GR,O'Donnell YEI,Shearer RF,Williams JT,Munoz AG,Cox TR,Watkins DN,Saunders DN,Timpson P,Lim E,Kolch W,Croucher

    更新日期:2019-03-21 00:00:00

  • HER-2 positive breast cancer: decreasing proportion but stable incidence in Finnish population from 1982 to 2005.

    abstract:INTRODUCTION:Classification of breast cancers according to the HER-2 oncogene status is of central importance in the selection of post-surgical therapies. A decrease in the proportion of HER-2-positive breast cancer has been suspected, but no data on the incidence trends at population level have been reported. METHODS...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2322

    authors: Köninki K,Tanner M,Auvinen A,Isola J

    更新日期:2009-01-01 00:00:00

  • Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

    abstract:INTRODUCTION:Mutations in BRCA1 and BRCA2 confer a high risk of breast cancer (BC), but the magnitude of this risk seems to vary according to the study and various factors. Although controversial, there are data to support the hypothesis of allelic risk heterogeneity. METHODS:We assessed variation in BC risk according...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr3218

    authors: Lecarpentier J,Noguès C,Mouret-Fourme E,Gauthier-Villars M,Lasset C,Fricker JP,Caron O,Stoppa-Lyonnet D,Berthet P,Faivre L,Bonadona V,Buecher B,Coupier I,Gladieff L,Gesta P,Eisinger F,Frénay M,Luporsi E,Lortholary A,

    更新日期:2012-07-03 00:00:00

  • Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the NG2 proteoglycan.

    abstract:INTRODUCTION:The neuron-glial antigen 2 (NG2) proteoglycan promotes pericyte recruitment and mediates pericyte interaction with endothelial cells. In the absence of NG2, blood vessel development is negatively impacted in several pathological models. Our goal in this study was to determine the effect of NG2 ablation on ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr3174

    authors: Gibby K,You WK,Kadoya K,Helgadottir H,Young LJ,Ellies LG,Chang Y,Cardiff RD,Stallcup WB

    更新日期:2012-04-24 00:00:00

  • Tamoxifen induces apoptosis through cancerous inhibitor of protein phosphatase 2A-dependent phospho-Akt inactivation in estrogen receptor-negative human breast cancer cells.

    abstract:INTRODUCTION:Tamoxifen, a selective estrogen receptor (ER) modulator, may affect cancer cell survival through mechanisms other than ER antagonism. In the present study, we tested the efficacy of tamoxifen in a panel of ER-negative breast cancer cell lines and examined the drug mechanism. METHODS:In total, five ER-nega...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-014-0431-9

    authors: Liu CY,Hung MH,Wang DS,Chu PY,Su JC,Teng TH,Huang CT,Chao TT,Wang CY,Shiau CW,Tseng LM,Chen KF

    更新日期:2014-09-17 00:00:00

  • An investigation of soy intake and mammographic characteristics in Hawaii.

    abstract::This cross-sectional investigation in Hawaii explored the relation between soy foods and mammographic characteristics using two food frequency questionnaires and a computer-assisted density assessment method. Japanese and Chinese women reported significantly greater soy food intake than Caucasian women. Whereas soy in...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr285

    authors: Maskarinec G,Meng L

    更新日期:2001-01-01 00:00:00

  • Tracking the genomic evolution of breast cancer metastasis.

    abstract::Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2469

    authors: Zecchin D,Bardelli A

    更新日期:2010-01-01 00:00:00

  • Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

    abstract:BACKGROUND:The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/s13058-017-0883-9

    authors: Toomey S,Eustace AJ,Fay J,Sheehan KM,Carr A,Milewska M,Madden SF,Teiserskiene A,Kay EW,O'Donovan N,Gallagher W,Grogan L,Breathnach O,Walshe J,Kelly C,Moulton B,Kennedy MJ,Gullo G,Hill AD,Power C,Duke D,Hambly N

    更新日期:2017-07-27 00:00:00

  • The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome.

    abstract:INTRODUCTION:Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1985

    authors: Butt AJ,Sergio CM,Inman CK,Anderson LR,McNeil CM,Russell AJ,Nousch M,Preiss T,Biankin AV,Sutherland RL,Musgrove EA

    更新日期:2008-01-01 00:00:00

  • Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3.

    abstract:INTRODUCTION:Metastasis is a common event and the main cause of death in cancer patients. Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to be involved in the development of metastasis. Sunitinib is a multi-kinase inhibitor that blocks receptor tyrosine kinase activity, including that...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr2903

    authors: Kodera Y,Katanasaka Y,Kitamura Y,Tsuda H,Nishio K,Tamura T,Koizumi F

    更新日期:2011-06-21 00:00:00

  • The pathology of familial breast cancer: Morphological aspects.

    abstract::A small proportion of breast cancers are due to a heritable predisposition. Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and cloned. The morphological features of tumours from patients harbouring mutations in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast cancers...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr10

    authors: Lakhani SR

    更新日期:1999-01-01 00:00:00

  • Update on the use of aromatase inhibitors in early-stage breast cancer.

    abstract::Aromatase inhibitors are currently included in the 'optimal' management of early-stage breast cancer. Uncertainty remains, however, as to the most appropriate treatment strategy, particularly for newly diagnosed women as they seek to trade off the cost, toxicities and efficacy of the treatment options. Recent publicat...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/bcr2410

    authors: Kesisis G,Makris A,Miles D

    更新日期:2009-01-01 00:00:00

  • CRIPTO antagonist ALK4L75A-Fc inhibits breast cancer cell plasticity and adaptation to stress.

    abstract:BACKGROUND:CRIPTO is a multi-functional signaling protein that promotes stemness and oncogenesis. We previously developed a CRIPTO antagonist, ALK4L75A-Fc, and showed that it causes loss of the stem cell phenotype in normal mammary epithelia suggesting it may similarly inhibit CRIPTO-dependent plasticity in breast canc...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-020-01361-z

    authors: Balcioglu O,Heinz RE,Freeman DW,Gates BL,Hagos BM,Booker E,Mirzaei Mehrabad E,Diesen HT,Bhakta K,Ranganathan S,Kachi M,Leblanc M,Gray PC,Spike BT

    更新日期:2020-11-13 00:00:00

  • The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis.

    abstract:INTRODUCTION:Matrix metalloproteinase (MMP)-2 is very active at degrading extracellular matrix. It is under the influence of an activator, membrane type 1 MMP (MMP-14), and the tissue inhibitor of metalloproteases (TIMP)-2. We hypothesized that the individual expression of these three markers or their balance may help ...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr1503

    authors: Têtu B,Brisson J,Wang CS,Lapointe H,Beaudry G,Blanchette C,Trudel D

    更新日期:2006-01-01 00:00:00

  • Ratios of involved nodes in early breast cancer.

    abstract:INTRODUCTION:The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that t...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/bcr934

    authors: Vinh-Hung V,Verschraegen C,Promish DI,Cserni G,Van de Steene J,Tai P,Vlastos G,Voordeckers M,Storme G,Royce M

    更新日期:2004-01-01 00:00:00

  • Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes.

    abstract:INTRODUCTION:Homologous recombination (HR) DNA repair is of clinical relevance in breast cancer. Three DNA-based homologous recombination deficiency (HRD) scores (HRD-loss of heterozygosity score (LOH), HRD-telomeric allelic imbalance score (TAI), and HRD-large-scale state transition score (LST)) have been developed th...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章

    doi:10.1186/s13058-014-0475-x

    authors: Timms KM,Abkevich V,Hughes E,Neff C,Reid J,Morris B,Kalva S,Potter J,Tran TV,Chen J,Iliev D,Sangale Z,Tikishvili E,Perry M,Zharkikh A,Gutin A,Lanchbury JS

    更新日期:2014-12-05 00:00:00

  • Raised mammographic density: causative mechanisms and biological consequences.

    abstract::High mammographic density is the most important risk factor for breast cancer, after ageing. However, the composition, architecture, and mechanical properties of high X-ray density soft tissues, and the causative mechanisms resulting in different mammographic densities, are not well described. Moreover, it is not know...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,评审

    doi:10.1186/s13058-016-0701-9

    authors: Sherratt MJ,McConnell JC,Streuli CH

    更新日期:2016-05-03 00:00:00

  • ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer.

    abstract:INTRODUCTION:Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas. METHODS:ER and H...

    journal_title:Breast cancer research : BCR

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/bcr3145

    authors: Pinhel I,Hills M,Drury S,Salter J,Sumo G,A'Hern R,Bliss JM,Sestak I,Cuzick J,Barrett-Lee P,Harris A,Dowsett M,NCRI Adjuvant Breast Cancer Trial Management Group.

    更新日期:2012-03-14 00:00:00