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 Cancerjournal_title
Molecular cancerauthors
Huang TS,Myklebust LM,Kjarland E,Gjertsen BT,Pendino F,Bruserud Ø,Døskeland SO,Lillehaug JRdoi
10.1186/1476-4598-6-31subject
Has Abstractpub_date
2007-04-23 00:00:00pages
31issn
1476-4598pii
1476-4598-6-31journal_volume
6pub_type
杂志文章相关文献
Molecular Cancer文献大全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
更新日期:2010-09-15 00:00:00
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
更新日期:2010-12-01 00:00:00
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
更新日期:2017-10-23 00:00:00
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
更新日期:2019-01-08 00:00:00
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
更新日期:2018-02-19 00:00:00
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
更新日期:2011-01-06 00:00:00
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
更新日期:2007-05-17 00:00:00
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
更新日期:2007-11-17 00:00:00
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
更新日期:2017-07-17 00:00:00
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
更新日期:2004-05-13 00:00:00
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
更新日期:2013-12-24 00:00:00
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
更新日期:2010-11-22 00:00:00
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
更新日期:2010-06-01 00:00:00
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
更新日期:2014-07-29 00:00:00
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
更新日期:2010-01-20 00:00:00
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
更新日期:2013-03-26 00:00:00
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
更新日期:2009-11-10 00:00:00
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
更新日期:2016-05-18 00:00:00
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
更新日期:2017-07-24 00:00:00
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
更新日期:2010-08-05 00:00:00
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
更新日期:2010-10-18 00:00:00
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
更新日期:2020-04-11 00:00:00
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
更新日期:2011-11-23 00:00:00
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
更新日期:2010-05-26 00:00:00
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
更新日期:2011-10-19 00:00:00
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
更新日期:2010-10-26 00:00:00
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
更新日期:2017-06-07 00:00:00
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
更新日期:2017-02-02 00:00:00
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
更新日期:2011-05-06 00:00:00
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
更新日期:2016-05-16 00:00:00