LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro.

Abstract:

BACKGROUND:Relapse due to chemoresistant residual disease is a major cause of death in acute myelogenous leukemia (AML). The present study was undertaken to elucidate the molecular mechanisms of chemoresistance by comparing differential gene expression in blasts from patients with resistant relapsing AML and chemosensitive AML. RESULTS:About 20 genes were identified as preferentially expressed in blasts pooled from patients with resistant disease, as compared to chemosensitive AML blasts, based on differential gene expression screening. Half of these genes encoded proteins related to protein translation, of these a novel protein related to the ribosomal stalk protein P0. Other upregulated mRNAs coded for cytochrome C oxidase III, the transcription factors ERF-2/TIS11d, and the p75 and p52 splice variants of Lens Epithelial Derived Growth Factor (LEDGF). Analysis of blasts from single patients disclosed that LEDGF/p75 was the most consistently upregulated mRNA in resistant AML. Transfection experiments demonstrated that LEDGF/p75 and p52b antagonized daunorubicin-induced and cAMP-induced apoptosis in an AML cell line. Also HEK-293 cells were protected against daunorubicin by LEDGF/p75 and p52b, whereas LEDGF/p52 splice variants lacking exon 6 had proapoptotic effects. Interestingly, full length LEDGF/p75 protected against truncated pro-apoptotic LEDGF/p75. CONCLUSION:Our results provide evidence for an association between the overexpression of genes encoding survival proteins like LEDGF/p75 and chemo-resistance in acute myelogenous leukemia. LEDGF/p75 has previously not been shown to protect against chemotherapy, and is a potential drug target in AML.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Huang TS,Myklebust LM,Kjarland E,Gjertsen BT,Pendino F,Bruserud Ø,Døskeland SO,Lillehaug JR

doi

10.1186/1476-4598-6-31

subject

Has Abstract

pub_date

2007-04-23 00:00:00

pages

31

issn

1476-4598

pii

1476-4598-6-31

journal_volume

6

pub_type

杂志文章
  • A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12.

    abstract::Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the ...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/1476-4598-9-242

    authors: Klinke DJ 2nd

    更新日期:2010-09-15 00:00:00

  • Broccoli, PTEN deletion and prostate cancer: where is the link?

    abstract::The concept that vegetables and fruits are relevant sources of cancer-preventive substances is strongly supported by population studies. Among others, cruciferous vegetables like broccoli, cabbage, cauliflower and Brussels sprouts are thought to affect the development of various types of cancers and especially prostat...

    journal_title:Molecular cancer

    pub_type: 评论,杂志文章

    doi:10.1186/1476-4598-9-308

    authors: Appendino G,Bardelli A

    更新日期:2010-12-01 00:00:00

  • Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a poor prognosis worldwide. While early stage tumours can be treated with curative approaches such as liver transplantation or surgical resection, these are only suitable for a minority of patients. Those with advanced stage disease are on...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-017-0734-4

    authors: Huo X,Han S,Wu G,Latchoumanin O,Zhou G,Hebbard L,George J,Qiao L

    更新日期:2017-10-23 00:00:00

  • The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression.

    abstract:BACKGROUND:In recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanis...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-018-0933-7

    authors: Yang R,Xing L,Zheng X,Sun Y,Wang X,Chen J

    更新日期:2019-01-08 00:00:00

  • Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.

    abstract::Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in ...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-018-0777-1

    authors: Wu SG,Shih JY

    更新日期:2018-02-19 00:00:00

  • Efficient TGF-β/SMAD signaling in human melanoma cells associated with high c-SKI/SnoN expression.

    abstract:BACKGROUND:SKI and SnoN proteins have been shown to inhibit TGF-β signaling, acting both as transcriptional co-repressors in the cell nucleus, and as sequestrators of SMAD proteins in the cytoplasm. TGF-β, on the other hand, induces rapid, proteasome-mediated, degradation of both proteins. How elevated SKI and SnoN pro...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-2

    authors: Javelaud D,van Kempen L,Alexaki VI,Le Scolan E,Luo K,Mauviel A

    更新日期:2011-01-06 00:00:00

  • A doxycycline-inducible urokinase receptor (uPAR) upregulates uPAR activities including resistance to anoikis in human prostate cancer cell lines.

    abstract:BACKGROUND:The urokinase receptor (uPAR) mediates a diverse array of cellular processes including several events involved in prostate cancer metastasis. Many of these activities are initiated or enhanced by uPAR binding to its proteolytic ligand, urokinase (uPA). Our objective in this study was to generate and test an ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-6-34

    authors: Hasanuzzaman M,Kutner R,Agha-Mohammadi S,Reiser J,Sehgal I

    更新日期:2007-05-17 00:00:00

  • The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells.

    abstract::Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing poten...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-6-73

    authors: Voortman J,Checińska A,Giaccone G

    更新日期:2007-11-17 00:00:00

  • Long non-coding RNA CASC2 suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis.

    abstract:BACKGROUND:Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-017-0702-z

    authors: Wang Y,Liu Z,Yao B,Li Q,Wang L,Wang C,Dou C,Xu M,Liu Q,Tu K

    更新日期:2017-07-17 00:00:00

  • Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells.

    abstract:BACKGROUND:The expression of the rodent phosphoinositide-specific phospholipase C delta-4 (PLCdelta4) has been found to be elevated upon mitogenic stimulation and expression analysis have linked the upregulation of PLCdelta4 expression with rapid proliferation in certain rat transformed cell lines. The human homologue ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-3-15

    authors: Leung DW,Tompkins C,Brewer J,Ball A,Coon M,Morris V,Waggoner D,Singer JW

    更新日期:2004-05-13 00:00:00

  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SIN1 association mediates ultraviolet B (UVB)-induced Akt Ser-473 phosphorylation and skin cell survival.

    abstract:BACKGROUND:The exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation. RESULTS:We found tha...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-12-172

    authors: Tu Y,Ji C,Yang B,Yang Z,Gu H,Lu CC,Wang R,Su ZL,Chen B,Sun WL,Xia JP,Bi ZG,He L

    更新日期:2013-12-24 00:00:00

  • The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine.

    abstract:BACKGROUND:Sigma-2 receptors are over-expressed in proliferating cancer cells, making an attractive target for the targeted treatment of pancreatic cancer. In this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to induce apoptosis and augment standard chemotherapy. RESULTS:The binding affini...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-298

    authors: Hornick JR,Xu J,Vangveravong S,Tu Z,Mitchem JB,Spitzer D,Goedegebuure P,Mach RH,Hawkins WG

    更新日期:2010-11-22 00:00:00

  • Knock down of HIF-1alpha in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres.

    abstract:BACKGROUND:Glioblastoma (GBM) is the most common and malignant primary intracranial human neoplasm. GBMs are characterized by the presence of extensive areas of necrosis and hypoxia. Hypoxia and its master regulator, hypoxia inducible factor 1 (HIF-1) play a key role in glioma invasion. RESULTS:To further elucidate th...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-133

    authors: Méndez O,Zavadil J,Esencay M,Lukyanov Y,Santovasi D,Wang SC,Newcomb EW,Zagzag D

    更新日期:2010-06-01 00:00:00

  • ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex.

    abstract:BACKGROUND:Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear. METHODS AND RESULTS:The ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-13-181

    authors: Zhang Q,Yang Z,Jia Z,Liu C,Guo C,Lu H,Chen P,Ma K,Wang W,Zhou C

    更新日期:2014-07-29 00:00:00

  • Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo.

    abstract:BACKGROUND:Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apop...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-10

    authors: Li X,Liu Y,Wen Z,Li C,Lu H,Tian M,Jin K,Sun L,Gao P,Yang E,Xu X,Kan S,Wang Z,Wang Y,Jin N

    更新日期:2010-01-20 00:00:00

  • MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1.

    abstract:BACKGROUND:Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive o...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-12-23

    authors: Creevey L,Ryan J,Harvey H,Bray IM,Meehan M,Khan AR,Stallings RL

    更新日期:2013-03-26 00:00:00

  • PTEN inhibits BMI1 function independently of its phosphatase activity.

    abstract:BACKGROUND:PTEN is the second most mutated tumor suppressor gene other than p53. It suppresses tumorigenesis by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate (PIP3) to phosphatidylinositol (4,5)-biphosphate (PIP2), thereby directly inhibiting phosphatidylinositol 3 kinase (PI3K)-mediated tumorigenic activ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-8-98

    authors: Fan C,He L,Kapoor A,Rybak AP,De Melo J,Cutz JC,Tang D

    更新日期:2009-11-10 00:00:00

  • Diagnostic, prognostic and predictive value of cell-free miRNAs in prostate cancer: a systematic review.

    abstract::Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolen...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-016-0523-5

    authors: Endzeliņš E,Melne V,Kalniņa Z,Lietuvietis V,Riekstiņa U,Llorente A,Linē A

    更新日期:2016-05-18 00:00:00

  • Role of long non-coding RNAs in glucose metabolism in cancer.

    abstract::Long-noncoding RNAs (lncRNAs) are a group of transcripts that are longer than 200 nucleotides and do not code for proteins. However, this class of RNAs plays pivotal regulatory roles. The mechanism of their action is highly complex. Mounting evidence shows that lncRNAs can regulate cancer onset and progression in a va...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-017-0699-3

    authors: Fan C,Tang Y,Wang J,Xiong F,Guo C,Wang Y,Zhang S,Gong Z,Wei F,Yang L,He Y,Zhou M,Li X,Li G,Xiong W,Zeng Z

    更新日期:2017-07-24 00:00:00

  • Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1.

    abstract:BACKGROUND:New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-209

    authors: Dhar K,Dhar G,Majumder M,Haque I,Mehta S,Van Veldhuizen PJ,Banerjee SK,Banerjee S

    更新日期:2010-08-05 00:00:00

  • Dasatinib reduces FAK phosphorylation increasing the effects of RPI-1 inhibition in a RET/PTC1-expressing cell line.

    abstract:BACKGROUND:TPC-1 is a papillary thyroid carcinoma (PTC)-derived cell line that spontaneously expresses the oncogene RET/PTC1. TPC-1 treated with the RET/PTC1 inhibitor RPI-1 displayed a cytostatic and reversible inhibition of cell proliferation and a strong activation of focal adhesion kinase (FAK). As dasatinib inhibi...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-278

    authors: Caccia D,Miccichè F,Cassinelli G,Mondellini P,Casalini P,Bongarzone I

    更新日期:2010-10-18 00:00:00

  • Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis.

    abstract::seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, whi...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-020-01195-5

    authors: Tan Y,Li Y,Tang F

    更新日期:2020-04-11 00:00:00

  • Anti-tumor effects of fibroblast growth factor-binding protein (FGF-BP) knockdown in colon carcinoma.

    abstract:BACKGROUND:Fibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM). One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP) which, upon reversible binding to FGF-1 or -2, leads to their relea...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-144

    authors: Schulze D,Plohmann P,Höbel S,Aigner A

    更新日期:2011-11-23 00:00:00

  • Targeting the Transforming Growth Factor-beta pathway inhibits human basal-like breast cancer metastasis.

    abstract:BACKGROUND:Transforming Growth Factor beta (TGF-beta) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-beta antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-beta pathway antagonists (...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-122

    authors: Ganapathy V,Ge R,Grazioli A,Xie W,Banach-Petrosky W,Kang Y,Lonning S,McPherson J,Yingling JM,Biswas S,Mundy GR,Reiss M

    更新日期:2010-05-26 00:00:00

  • Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces.

    abstract:BACKGROUND:Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-131

    authors: Asteriti IA,Giubettini M,Lavia P,Guarguaglini G

    更新日期:2011-10-19 00:00:00

  • IGFBP-rP1, a potential molecule associated with colon cancer differentiation.

    abstract:BACKGROUND:In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer ...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-9-281

    authors: Ruan W,Zhu S,Wang H,Xu F,Deng H,Ma Y,Lai M

    更新日期:2010-10-26 00:00:00

  • Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development.

    abstract::Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the p...

    journal_title:Molecular cancer

    pub_type: 杂志文章,评审

    doi:10.1186/s12943-017-0670-3

    authors: Zhao HF,Wang J,Shao W,Wu CP,Chen ZP,To ST,Li WP

    更新日期:2017-06-07 00:00:00

  • Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer.

    abstract:BACKGROUND:Colorectal cancer is third most common malignancy and is the second most common cause of cancer-related death. The MUC1 heterodimeric protein is aberrantly overexpressed in colorectal cancer and has been linked to poor outcomes in this disease. Here, we investigate the effects of the MUC1-C subunit inhibitor...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-017-0608-9

    authors: Ahmad R,Alam M,Hasegawa M,Uchida Y,Al-Obaid O,Kharbanda S,Kufe D

    更新日期:2017-02-02 00:00:00

  • Regulation of PBX3 expression by androgen and Let-7d in prostate cancer.

    abstract:BACKGROUND:The pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of th...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/1476-4598-10-50

    authors: Ramberg H,Alshbib A,Berge V,Svindland A,Taskén KA

    更新日期:2011-05-06 00:00:00

  • Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib.

    abstract:BACKGROUND:Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking. METHODS:We used gen...

    journal_title:Molecular cancer

    pub_type: 杂志文章

    doi:10.1186/s12943-016-0526-2

    authors: Houessinon A,François C,Sauzay C,Louandre C,Mongelard G,Godin C,Bodeau S,Takahashi S,Saidak Z,Gutierrez L,Régimbeau JM,Barget N,Barbare JC,Ganne N,Chauffert B,Coriat R,Galmiche A

    更新日期:2016-05-16 00:00:00