Abstract:
:In this study, we investigated the regulation of FOXM1 expression by estrogen receptor alpha (ERalpha) and its role in hormonal therapy and endocrine resistance. FOXM1 protein and mRNA expression was regulated by ER-ligands, including estrogen, tamoxifen (OHT) and fulvestrant (ICI182780; ICI) in breast carcinoma cell lines. Depletion of ERalpha by RNA interference (RNAi) in MCF-7 cells downregulated FOXM1 expression. Reporter gene assays showed that ERalpha activates FOXM1 transcription through an estrogen-response element (ERE) located within the proximal promoter region. The direct binding of ERalpha to the FOXM1 promoter was confirmed in vitro by mobility shift and DNA pull-down assays and in vivo by chromatin immunoprecipitation (ChIP) analysis. Our data also revealed that upon OHT treatment ERalpha recruits histone deacetylases to the ERE site of the FOXM1 promoter, which is associated with a decrease in histone acetylation and transcription activity. Importantly, silencing of FOXM1 by RNAi abolished estrogen-induced MCF-7 cell proliferation and overcame acquired tamoxifen resistance. Conversely, ectopic expression of FOXM1 abrogated the cell cycle arrest mediated by the anti-estrogen OHT. OHT repressed FOXM1 expression in endocrine sensitive but not resistant breast carcinoma cell lines. Furthermore, qRT-PCR analysis of breast cancer patient samples revealed that there was a strong and significant positive correlation between ERalpha and FOXM1 mRNA expression. Collectively, these results show FOXM1 to be a key mediator of the mitogenic functions of ERalpha and estrogen in breast cancer cells, and also suggest that the deregulation of FOXM1 may contribute to anti-estrogen insensitivity.
journal_name
Oncogenejournal_title
Oncogeneauthors
Millour J,Constantinidou D,Stavropoulou AV,Wilson MS,Myatt SS,Kwok JM,Sivanandan K,Coombes RC,Medema RH,Hartman J,Lykkesfeldt AE,Lam EWdoi
10.1038/onc.2010.47subject
Has Abstractpub_date
2010-05-20 00:00:00pages
2983-95issue
20eissn
0950-9232issn
1476-5594pii
onc201047journal_volume
29pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Immunological screening with the anti-p53 moAb, PAb1801 of a cDNA expression library, prepared from human B lymphoma cells, led us to identify a new human 205 kDa protein called RB18A for 'Recognized By PAb1801 moAntibody'. Immunoblotting or immunoprecipitation of fusion protein or in vitro translated protein, respect...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201492
更新日期:1997-12-18 00:00:00
abstract::Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regul...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.296
更新日期:2014-06-19 00:00:00
abstract::Breast cancer cells that overexpress HER-2/neu are more resistant to chemotherapeutic agents such as paclitaxel (Taxol) and docetaxel (Taxotere) than those that do not overexpress HER-2/neu. In previous work, we showed that the adenovirus type 5 E1A can repress HER-2/neu expression at the transcriptional level. Here w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201250
更新日期:1997-08-18 00:00:00
abstract::Receptor tyrosine kinases of the Eph family are upregulated in several different types of cancer. One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma. However, mechanisms by which EphA2 contributes to tumor progression are far from clear....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208937
更新日期:2005-11-24 00:00:00
abstract::RING-finger proteins play crucial roles in ubiquitination events involved in diverse cellular processes including signal transduction, differentiation and apoptosis. Most of the RING-finger proteins have E3-ubiquitin ligase activity. RNF11 is a small RING-finger protein and harbors a RING-H2 domain and a PY motif that...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207319
更新日期:2004-03-11 00:00:00
abstract::Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and nonirradiated cells in the population. This phenomenon, termed the 'bystander response', has been shown to occur both in vi...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1206961
更新日期:2003-10-13 00:00:00
abstract::Skeletrophin (mindbomb homolog 2 (MIB2)) is a RING (Really Interesting New Gene) finger-dependent ubiquitin ligase, which targets the intracellular region of Notch ligands. A previous immunohistochemical study demonstrated that skeletrophin was downregulated in many melanomas. In the present study, we have identified ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209688
更新日期:2006-11-09 00:00:00
abstract::Degradation of chromosomal DNA into nucleosome-sized fragments is one of the characteristics of apoptotic cell death. Here, we examined whether caspase-activated DNase (CAD) is responsible for the DNA fragmentation that occurs upon exposure to various apoptotic stimuli. When human Jurkat cells were exposed to etoposid...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202868
更新日期:1999-08-05 00:00:00
abstract::A33 antigen is a membrane-bound protein that is expressed only in intestinal epithelium and in most human colon cancers. Thus, A33 antigen has been explored as a potential therapeutic target for the treatment of colon cancers. However, little is known about the mechanism responsible for the tissue-specific pattern of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206508
更新日期:2003-07-10 00:00:00
abstract::Previous studies have shown that the cell cycle-regulated B-myb promoter contains a conserved E2F binding site that is critical for repressing transcription in quiescent cells. To investigate its significance for permanent promoter silencing, we have inactivated this binding site in the mouse genome. Mice homozygous f...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210087
更新日期:2007-04-26 00:00:00
abstract::The oncogene, v-rel is a member of the rel/NF-kappaB family of transcription factors. It causes a rapidly fatal lymphoma in young chicks and is capable of transforming both fibroblasts and primitive hematopoietic cells in culture. To understand the role of v-rel in transformation we constructed an inducible form of v-...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-06-20 00:00:00
abstract::Complementary DNA (cDNA) encoding a novel member of the receptor tyrosine kinase (RTK) family has been isolated from colon carcinoma tissue. Colon carcinoma kinase 4 (CCK-4) mRNA is highly expressed in human lung tissue and at lower levels in the thyroid gland and ovary. While no mRNA was found in human adult colon ti...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::Guanine nucleotide binding protein-like 3-like (GNL3L) is a nucleolar protein and the vertebrate paralogue of nucleostemin (NS). We previously reported that nucleoplasmic mobilization of NS stabilizes MDM2 (mouse double minute 2). Here, we investigated the role of GNL3L as a novel MDM2 regulator. We found that GNL3L b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.550
更新日期:2011-04-07 00:00:00
abstract::Several cytokines, growth factors and the HIV transactivator Tat were shown to be involved in the pathogenesis of Kaposi's sarcoma. BKV/tat transgenic mice develop Kaposi's sarcoma-like lesions, and spindle-shaped cells (TTB) have been derived from these lesions. Here we show that TTB cells co-express hepatocyte growt...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-09-05 00:00:00
abstract::Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207181
更新日期:2003-11-27 00:00:00
abstract::Exposure of cells to DNA damaging agents results in a G2 arrest. Exposure of HeLa cells to camptothecin, etoposide or nitrogen mustard for 1 h in S phase resulted in delayed expression of cyclin B1 mRNA during the G2 arrest. Initially the levels of cyclin B1 protein were low as well; however, with extended time the ce...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-10-17 00:00:00
abstract::Knowledge of the type of biological reaction to chemotherapy is a prerequisite for its rational enhancement. We previously showed that irinotecan-induced DNA damage triggers in the HCT116p53(wt) colon carcinoma cell line a long-term cell cycle arrest and in HCT116p53(-/-) cells apoptosis (Magrini et al., 2002). To com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209017
更新日期:2006-01-12 00:00:00
abstract::The Mucin 1 (MUC1) protein is overexpressed in various cancers and mediates chemotherapy resistance. However, the mechanism is not fully understood. Given that most chemotherapeutic drugs disrupt ER homeostasis as part of their toxicity, and MUC1 expression is regulated by proteins involved in ER homeostasis, we inves...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1225-4
更新日期:2020-04-01 00:00:00
abstract::Since defects in molecular mechanisms controlling DNA repair, cell cycle checkpoint and apoptosis could modify cellular sensitivity to DNA damaging agents, we have conducted a multiparametric molecular analysis for better understanding the regulation pathways leading to cell survival or cell death after irradiation. U...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203405
更新日期:2000-02-17 00:00:00
abstract::Heat shock protein 70 (HSP70) can inhibit apoptosis by neutralizing and interacting with apoptosis-inducing factor (AIF), a mitochondrial flavoprotein that translocates upon apoptosis induction to the nucleus, via the cytosol. Here, we show that only members of the HSP70 family interact with AIF. Systematic deletion m...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206794
更新日期:2003-10-02 00:00:00
abstract::Human papillomaviruses are the causative agents of cervical cancer. Previous studies have shown that loss of the viral E2 protein during malignant progression is an important feature of HPV-induced malignancy due to the resulting uncontrolled expression of the viral oncoproteins E6 and E7. We now show however that the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208701
更新日期:2005-08-04 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by an accumulation of immature T cells. Although patient outcomes have improved, novel targeted therapies are needed to reduce the intensity of chemotherapy and improve the prognosis of high-risk patients. Interleukin-7...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0921-4
更新日期:2019-11-01 00:00:00
abstract::Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell l...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01517-3
更新日期:2021-01-01 00:00:00
abstract::The heterodimeric nuclear factor (NF) 90/NF45 complex (NF90/NF45) binds nucleic acids and is a multifunctional regulator of gene expression. Here we report that depletion of NF90/NF45 restores the expression of the p53 and p21 proteins in cervical carcinoma cells infected with high-risk human papillomaviruses (HPVs). ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.533
更新日期:2013-10-24 00:00:00
abstract::Activation of cellular transcriptional responses, mediated by hypoxia-inducible factor (HIF), is common in many types of cancer, and generally confers a poor prognosis. Known to induce many hundreds of protein-coding genes, HIF has also recently been shown to be a key regulator of the non-coding transcriptional respon...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.378
更新日期:2015-08-20 00:00:00
abstract::There is now much evidence to suggest that the p53 tumour suppressor protein functions to monitor the integrity of the genome. When DNA damage is detected, p53 suppresses cell growth to allow repair or directs the cell into apoptosis. The mechanism of action of p53 is as yet unclear but recent evidence has accumulated...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-10-05 00:00:00
abstract::Ras genes, frequently mutated in human tumors, promote malignant transformation. Ras transformation requires membrane anchorage, which is promoted by Ras farnesylcysteine carboxymethylester and by a second signal. Previously we showed that the farnesylcysteine mimetic, farnesylthiosalicylic acid (FTS) disrupts Ras mem...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204950
更新日期:2001-11-08 00:00:00
abstract::Testicular germ cell tumours are classified into two major histological subgroups, seminomas and nonseminomas. All tumours display several recurrent chromosomal aberrations, but few target genes have been identified. Previous studies have shown that genome-wide hypermethylation of CpG islands is significantly more pre...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205978
更新日期:2002-12-12 00:00:00
abstract::ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is frequently associated with an aggressive clinical course of certain human adenocarcinomas, t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201029
更新日期:1997-05-01 00:00:00
abstract::Targeted therapeutics are potential therapeutic agents because of their selectivity and efficacy against tumors resistant to conventional therapy. The goal of this study was to determine the comparative activity of monovalent, engineered anti-Her2/neu immunotoxins fused to recombinant gelonin (rGel) to the activity of...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.612
更新日期:2014-01-23 00:00:00