The role of Tcfap2c in tumorigenesis and cancer growth in an activated Neu model of mammary carcinogenesis.


:TFAP2C/AP-2γ influences development of the mammary gland and regulates patterns of gene expression in luminal and HER2-amplified breast cancer. The roles of TFAP2C in mammary gland tumorigenesis and in pathways critical to cancer progression remain poorly understood. To gain greater insight into oncogenic mechanisms regulated by TFAP2C, we examined mammary tumorigenesis in MMTV-Neu transgenic female mice with or without conditional knockout (KO) of Tcfap2c, the mouse homolog of TFAP2C. Loss of Tcfap2c increased the latency of tumorigenesis and tumors that formed demonstrated reduced proliferative index and increased apoptosis. In addition, tumors formed in Tcfap2c KO animals had a significant reduction in Egfr levels without a change in the expression of the Neu oncogene. The MMneu-flAP2C cell line was established from tumor tissue derived from MMTV-Neu/Tcfap2c(L/L) control animals and parallel cell lines with and without expression of Tcfap2c were created by transduction with adenovirus-empty and adenovirus-Cre, respectively. KO of Tcfap2c in vitro reduced activated phosphorylated-Erk, decreased cell viability, repressed tumor growth and was associated with attenuation of Egfr expression. Chromatin immunoprecipitation and direct sequencing and expression analysis confirmed that Egfr was a Tcfap2c target gene in murine, as well as human, mammary carcinoma cells. Furthermore, decreased viability of mammary cancer cells was directly related to Egfr functional blockade. We conclude that TFAP2C regulates tumorigenesis, cell growth and survival in HER2-amplified breast cancer through transcriptional regulation of EGFR. The findings have important implications for targeting the EGFR pathway in breast cancer.






Park JM,Wu T,Cyr AR,Woodfield GW,De Andrade JP,Spanheimer PM,Li T,Sugg SL,Lal G,Domann FE,Zhang W,Weigel RJ




Has Abstract


2015-12-10 00:00:00
















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    abstract::The stress-activated pathways leading to activation of p38 MAP kinase (p38 MAPK) and c-jun N-terminal kinases (JNK) have been shown to be activated by pro-inflammatory cytokines, physical and chemical stresses as well as a variety of hematopoietic growth factors. One exception is interleukin (IL)-4, which does not act...


    pub_type: 杂志文章


    authors: Wery-Zennaro S,Zugaza JL,Letourneur M,Bertoglio J,Pierre J

    更新日期:2000-03-16 00:00:00

  • KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties.

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    pub_type: 杂志文章


    authors: Saha SK,Choi HY,Kim BW,Dayem AA,Yang GM,Kim KS,Yin YF,Cho SG

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  • Epigenetic regulations in hematopoietic Hox code.

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    pub_type: 杂志文章,评审


    authors: He H,Hua X,Yan J

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  • DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

    abstract::Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription ...


    pub_type: 杂志文章


    authors: Moon SJ,Jeong BC,Kim HJ,Lim JE,Kwon GY,Kim JH

    更新日期:2018-03-01 00:00:00

  • Molecular characterization and modular analysis of human MyD88.

    abstract::MyD88 was first characterized as a myeloid differentiation primary response gene in mice, activated in M1 myeloleukemic cells following interleukin-6 (IL-6) induced growth arrest and terminal differentiation. Analysis of expressed sequence tags (ESTs) from activated dendritic cell libraries led to the indentification ...


    pub_type: 杂志文章


    authors: Hardiman G,Rock FL,Balasubramanian S,Kastelein RA,Bazan JF

    更新日期:1996-12-05 00:00:00

  • Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas.

    abstract::Malignant glioma represents one of the most aggressive and lethal human neoplasias. A hallmark of gliomas is their rapid proliferation and destruction of vital brain tissue, a process in which excessive glutamate release by glioma cells takes center stage. Pharmacologic antagonism with glutamate signaling through iono...


    pub_type: 杂志文章


    authors: Savaskan NE,Seufert S,Hauke J,Tränkle C,Eyüpoglu IY,Hahnen E

    更新日期:2011-01-06 00:00:00

  • Regulation of MET receptor tyrosine kinase signaling by suppressor of cytokine signaling 1 in hepatocellular carcinoma.

    abstract::Suppressor of cytokine signaling 1 (SOCS1) is considered as a tumor suppressor protein in hepatocellular carcinoma (HCC), but the underlying mechanisms remain unclear. Previously, we have shown that SOCS1-deficient hepatocytes displayed increased responsiveness to hepatocyte growth factor (HGF) due to enhanced signali...


    pub_type: 杂志文章


    authors: Gui Y,Yeganeh M,Donates YC,Tobelaim WS,Chababi W,Mayhue M,Yoshimura A,Ramanathan S,Saucier C,Ilangumaran S

    更新日期:2015-11-12 00:00:00

  • The mouse soluble GFRalpha4 receptor activates RET independently of its ligand persephin.

    abstract::Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) all signal through the transmembrane receptor tyrosine kinase RET. The signalling complex consists of GFLs, GPI-anchored ligand binding GDNF family receptor alphas (GFRalphas) and RET. Signalling via RET is required for the development of the ner...


    pub_type: 杂志文章


    authors: Yang J,Runeberg-Roos P,Leppänen VM,Saarma M

    更新日期:2007-05-31 00:00:00

  • The lncRNA BORG facilitates the survival and chemoresistance of triple-negative breast cancers.

    abstract::Disseminated breast cancer cells employ adaptive molecular responses following cytotoxic therapeutic insult which promotes their survival and subsequent outgrowth. Here we demonstrate that expression of the pro-metastatic lncRNA BORG (BMP/OP-Responsive Gene) is greatly induced within triple-negative breast cancer (TNB...


    pub_type: 杂志文章


    authors: Gooding AJ,Zhang B,Gunawardane L,Beard A,Valadkhan S,Schiemann WP

    更新日期:2019-03-01 00:00:00

  • The human papillomavirus type 16 (HPV-16) E5 protein sensitizes human keratinocytes to apoptosis induced by osmotic stress.

    abstract::We have studied the role of the HPV-16 E5 protein in apoptosis, using HaCaT cell lines stably transfected with either E5 (HaCaT/E5) or the empty vector (HaCaT/pMSG) as control. When subjected to a hyperosmolar concentration of sorbitol, HaCaT/E5 cells respond with cytochrome c release, activation of caspase-3, -8, and...


    pub_type: 杂志文章


    authors: Kabsch K,Alonso A

    更新日期:2002-01-31 00:00:00

  • The adenovirus E1A 289R and 243R proteins inhibit the phosphorylation of p300.

    abstract::A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A...


    pub_type: 杂志文章


    authors: Banerjee AC,Recupero AJ,Mal A,Piotrkowski AM,Wang DM,Harter ML

    更新日期:1994-06-01 00:00:00

  • Amplification of N-myc and ornithine decarboxylase genes in human neuroblastoma and hydroxyurea-resistant hamster cell lines.

    abstract::The genes for the M2 subunit of ribonucleotide reductase (RRM2), ornithine decarboxylase (ODC1), and 55,000-Daltons protein (P5), are amplified in hydroxyurea-resistant hamster and human cell lines. These genomic sequences have been mapped to hamster chromosome 7 and to human chromosome 2p24-25 near the cytogenetic lo...


    pub_type: 杂志文章


    authors: Tonin PN,Yeger H,Stallings RL,Srinivasan PR,Lewis WH

    更新日期:1989-09-01 00:00:00

  • A new form of RET rearrangement in thyroid carcinomas of children after the Chernobyl reactor accident.

    abstract::Intrachromosomal rearrangements involving the RET and the adjacent H4 or ELE1 gene are very frequent events in thyroid cancer of children from Belarus after the Chernobyl reactor accident (Klugbauer et al., 1995). The fusion product between ELE1 and RET (RET/ PTC3) seems to be the prevailing type of rearrangement as s...


    pub_type: 杂志文章


    authors: Klugbauer S,Lengfelder E,Demidchik EP,Rabes HM

    更新日期:1996-09-05 00:00:00

  • Restoration of p53 expression sensitizes human papillomavirus type 16 immortalized human keratinocytes to CD95-mediated apoptosis.

    abstract::To understand the function of the individual oncogenes of HPV16 in modulating the cellular response to apoptogenic signals, we used human keratinocytes immortalized with either E6, E7 or E6/E7 oncoproteins as model system. Applying CD95 antibodies or recombinant CD95 ligand, only the E7-immortalized cells underwent ex...


    pub_type: 杂志文章


    authors: Aguilar-Lemarroy A,Gariglio P,Whitaker NJ,Eichhorst ST,zur Hausen H,Krammer PH,Rösl F

    更新日期:2002-01-10 00:00:00

  • Overexpression of p21WAF1/CIP1 induces growth arrest, giant cell formation and apoptosis in human breast carcinoma cell lines.

    abstract::The p21WAF1/CIP1 protein was shown to be a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. We investigated the effects of exogenous p21WAF1/CIP1 in two different human breast carcinoma (HBC) cell lines MCF-7 and T47D. p21WAF1/CIP1 transfected cells formed significantly reduced n...


    pub_type: 杂志文章


    authors: Sheikh MS,Rochefort H,Garcia M

    更新日期:1995-11-02 00:00:00

  • The E3 ubiquitin protein ligase MDM2 dictates all-trans retinoic acid-induced osteoblastic differentiation of osteosarcoma cells by modulating the degradation of RARα.

    abstract::Retinoic acid receptor alpha (RARα) has a critical role in the differentiation process of osteosarcoma cells induced by all-trans retinoic acid (ATRA). However, degradation of RARα through ubiquitin proteasome pathway weakens the differentiation efficiency of osteosarcoma cells. In this study, we discover that murine ...


    pub_type: 杂志文章


    authors: Ying M,Zhang L,Zhou Q,Shao X,Cao J,Zhang N,Li W,Zhu H,Yang B,He Q

    更新日期:2016-08-18 00:00:00

  • Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency.

    abstract::Genetically defined mouse models offer an important tool to identify critical secondary genetic alterations with relevance to human cancer pathogenesis. We used newly generated MMTV-Cre105Ayn mice to inactivate p53 and/or Rb strictly in the mammary epithelium, and to determine recurrent genomic changes associated with...


    pub_type: 杂志文章


    authors: Cheng L,Zhou Z,Flesken-Nikitin A,Toshkov IA,Wang W,Camps J,Ried T,Nikitin AY

    更新日期:2010-10-21 00:00:00

  • Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma.

    abstract::We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions an...


    pub_type: 杂志文章


    authors: El-Naggar AK,Coombes MM,Batsakis JG,Hong WK,Goepfert H,Kagan J

    更新日期:1998-06-11 00:00:00

  • Cell type-specific responses of human cells to inhibition of replication licensing.

    abstract::Replication origins are 'licensed' for a single initiation event by loading Mcm2-7 complexes during late mitosis and G1. Licensing is blocked at other cell cycle stages by the activity of cyclin-dependent kinases and a small protein called geminin. Here, we describe the effects of over-expressing a non-degradable form...


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    authors: Shreeram S,Sparks A,Lane DP,Blow JJ

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  • CFP suppresses breast cancer cell growth by TES-mediated upregulation of the transcription factor DDIT3.

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    pub_type: 杂志文章


    authors: Block I,Müller C,Sdogati D,Pedersen H,List M,Jaskot AM,Syse SD,Lund Hansen P,Schmidt S,Christiansen H,Casella C,Bering Olsen S,Blomstrøm MM,Riedel A,Thomassen M,Kruse TA,Karlskov Hansen SW,Kioschis P,Mollenhauer J

    更新日期:2019-06-01 00:00:00

  • Sin3a acts through a multi-gene module to regulate invasion in Drosophila and human tumors.

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    authors: Das TK,Sangodkar J,Negre N,Narla G,Cagan RL

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  • The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells.

    abstract::Vascular endothelial growth factor (VEGF) production by stromal fibroblasts plays an important role in tumor angiogenesis. However, VEGF is also expressed by normal tissue fibroblasts, raising the question of how the VEGF activity of fibroblasts is regulated. Here we report that the latent VEGF angiogenic activity of ...


    pub_type: 杂志文章


    authors: Ito TK,Ishii G,Chiba H,Ochiai A

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  • The DNA-damage response and nuclear events as regulators of nonapoptotic forms of cell death.

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    pub_type: 杂志文章,评审


    authors: Prokhorova EA,Egorshina AY,Zhivotovsky B,Kopeina GS

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    pub_type: 杂志文章


    authors: Chen Q,Ash JD,Branton P,Fromm L,Overbeek PA

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    pub_type: 杂志文章,评审


    authors: Launay S,Hermine O,Fontenay M,Kroemer G,Solary E,Garrido C

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  • Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis.

    abstract::Jun : Fos and Jun : ATF complexes represent two classes of AP-1 dimers that (1) preferentially bind to either heptameric or octameric AP-1 binding sites, and (2) are differently regulated by cellular signaling pathways and oncogene products. To discriminate between the functions of Jun : Fos, Jun : ATF and Jun : Jun, ...


    pub_type: 杂志文章,评审


    authors: van Dam H,Castellazzi M

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  • Somatic VHL gene deletion and point mutation in MEN 2A-associated pheochromocytoma.

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    pub_type: 杂志文章


    authors: Koch CA,Huang SC,Zhuang Z,Stolle C,Azumi N,Chrousos GP,Vortmeyer AO,Pacak K

    更新日期:2002-01-17 00:00:00

  • Microsatellite instability in prostate cancer.

    abstract::Assessment of the genetic instability of a microsatellite has indicated a new mechanism in human carcinogenesis. Examination was made to determine whether microsatellite instability is associated with the onset of prostate cancer. Twenty-nine DNA samples from 24 primary prostate cancer, two metastatic lymph-node and t...


    pub_type: 杂志文章


    authors: Uchida T,Wada C,Wang C,Ishida H,Egawa S,Yokoyama E,Ohtani H,Koshiba K

    更新日期:1995-03-02 00:00:00

  • Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous cell carcinoma.

    abstract::We have shown earlier that overexpression of Calreticulin (CRT) contributed to a poor prognosis for patients with esophageal squamous cell carcinoma (ESCC). Here, we have shown an important role of CRT in tumorigenesis through enhancing cell motility and anoikis resistance. SiRNA-mediated knockdown of CRT caused impai...


    pub_type: 杂志文章


    authors: Du XL,Yang H,Liu SG,Luo ML,Hao JJ,Zhang Y,Lin DC,Xu X,Cai Y,Zhan QM,Wang MR

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  • All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo.

    abstract::Wilms tumor is one of the most frequent neoplasias in children. Our previous microarray screening in a large series of Wilms tumors revealed several candidate genes that are deregulated in advanced tumors and are part of the retinoic acid signaling pathway. To investigate whether retinoic acid could be employed as a n...


    pub_type: 杂志文章


    authors: Zirn B,Samans B,Spangenberg C,Graf N,Eilers M,Gessler M

    更新日期:2005-08-04 00:00:00