Abstract:
:The efficacy of anticancer therapy is limited by the development of drug resistance. While the role of p53 in the intrinsic sensitivity of human cancer cells to paclitaxel (PTX) remains controversial, its role in acquired paclitaxel resistance has never been addressed. In this study we examined the p53 status of three paclitaxel selected human ovarian carcinoma sublines, resistant to paclitaxel due to acquired beta-tubulin mutations which impair paclitaxel's interaction with tubulin. In contrast to parental cells which have wt p53, in all PTX-resistant sublines p53 was functionally inactive. Two of the resistant sublines expressed high levels of transcriptionally inactive p53 protein, each with a distinct point mutation in codons 236 and 239 of the DNA binding domain. The third subline presented a novel p53 pseudo-null phenotype as a result of markedly decreased wt p53 mRNA expression. Introduction of ectopic wt p53 had no effect on PTX sensitivity in both parental and resistant cells, while it induced p21WAF1/CIP1, demonstrating an intact p53 pathway. While PTX resistance is primarily conferred by the tubulin mutations, the loss of functional p53 observed in all clones, suggests that this loss may facilitate the development of resistance potentially by providing a clonal advantage which promotes the isolation of paclitaxel resistant cells.
journal_name
Oncogenejournal_title
Oncogeneauthors
Giannakakou P,Poy G,Zhan Z,Knutsen T,Blagosklonny MV,Fojo Tdoi
10.1038/sj.onc.1203642subject
Has Abstractpub_date
2000-06-22 00:00:00pages
3078-85issue
27eissn
0950-9232issn
1476-5594journal_volume
19pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Augmented reactive oxygen species levels consequential to functional alteration of key mitochondrial attributes contribute to carcinogenesis, either directly via oxidative DNA damage infliction or indirectly via activation of oncogenic signaling cascades. We previously reported activation of a key oncogenic signaling ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.346
更新日期:2017-03-30 00:00:00
abstract::Predisposition to melanoma is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on ident...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1206445
更新日期:2003-05-19 00:00:00
abstract::Cells in culture become competent to replicate in the absence of growth factor after progressing beyond the late G1 restriction point, suggesting that a set of genes expressed during G1 phase is sufficient to trigger completion of the cell cycle. However, this has not been demonstrated in an in vivo system. In this st...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204248
更新日期:2001-04-05 00:00:00
abstract::Deregulation of Wnt signalling has recently been implicated in human renal cancer. Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium. Mice homozygous for a conditional Apc allele were intercrossed with mice transg...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208956
更新日期:2005-12-08 00:00:00
abstract::Bone metastatic prostate cancer provokes extensive osteogenesis by driving the recruitment and osteoblastic differentiation of mesenchymal stromal cells (MSCs). The resulting lesions greatly contribute to patient morbidity and mortality, underscoring the need for defining how prostate metastases subvert the MSC-osteob...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0913-4
更新日期:2019-10-01 00:00:00
abstract::Protein kinase D2 (PKD2) is a serine/threonine kinase that belongs to the PKD family of calcium-calmodulin kinases, which comprises three isoforms: PKD1, PKD2, and PKD3. PKD2 is activated by many stimuli including growth factors, phorbol esters, and G-protein-coupled receptor agonists. PKD2 participation to uncontroll...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/s41388-017-0052-8
更新日期:2018-03-01 00:00:00
abstract::Burkitt's lymphoma cells are characterized by chromosomal translocations involving the proto-oncogene c-myc on chromosome 8 and one of the immunoglobulin gene loci on chromosome 2, 14 or 22. The translocated c-myc allele is transcriptionally activated, shows a preferential usage of promoter P1 over P2 (promoter shift)...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-04-06 00:00:00
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...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts. In contrast, MCP-1 transcription is absent in tumor...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203643
更新日期:2000-07-06 00:00:00
abstract::The mechanisms by which the p53 tumour suppressor protein would, in vivo, co-ordinate the adaptive response to genotoxic stress is poorly understood. p53 has been shown to transactivate several genes that could be involved in two main cellular responses, growth arrest and apoptosis. To get further insight into the tis...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203366
更新日期:2000-02-03 00:00:00
abstract::The aspartic protease cathepsin D (cath-D) is a key mediator of induced-apoptosis and its proteolytic activity has been generally involved in this event. During apoptosis, cath-D is translocated to the cytosol. Because cath-D is one of the lysosomal enzymes that requires a more acidic pH to be proteolytically active r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209221
更新日期:2006-03-23 00:00:00
abstract::Transforming growth factor alpha (TGFalpha) is widely expressed in malignant as well as normal cells and is involved in regulating cell growth and differentiation. Although processing of TGFalpha has been extensively studied in normal cells, there is little information regarding TGFalpha cleavage in malignant cells. T...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203513
更新日期:2000-04-06 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is as...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.481
更新日期:2016-08-04 00:00:00
abstract::To understand the mechanism of interferon (IFN)-mediated suppression of cell cycle progression, we have earlier shown that IFN-alpha enhances the expression of underphosphorylated retinoblastoma protein by inhibiting the cyclin-dependent kinase-2 (CDK-2) activity (Kumar and Atlas, Proc. Natl. Acad. Sci. 89, 6599-6603,...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201529
更新日期:1998-01-15 00:00:00
abstract::Activation of the Akt/PKB protein kinase family triggers increases in cell size, metabolism and survival. Akt coordinately regulates these fundamental cellular processes through phosphorylation-dependent inactivation of tumor suppressors and activation of trophic signaling. Akt signaling stimulates transport and metab...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209097
更新日期:2005-11-14 00:00:00
abstract::RAS is a small GTP binding protein mutated in approximately 30% human cancer. Despite its important role in the initiation and progression of human cancer, the underlying mechanism of RAS-induced human epithelial transformation remains elusive. In this study, we probe the cellular and molecular mechanisms of RAS-media...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208753
更新日期:2005-09-08 00:00:00
abstract::Treatment of many cancers relies on the combined action of several genotoxins, but the detrimental effect of these drugs on normal cells can cause severe side effects. One major challenge in anticancer therapy is therefore to increase the selectivity of current treatments toward cancer cells in order to spare normal c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207999
更新日期:2004-11-25 00:00:00
abstract::Treatment options for adenoid cystic carcinoma (ACC) of the salivary gland, a slowly growing tumor with propensity for neuroinvasion and late recurrence, are limited to surgery and radiotherapy. Based on expression analysis performed on clinical specimens of salivary cancers, we identified in ACC expression of the neu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.377
更新日期:2013-08-08 00:00:00
abstract::ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contain...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-01-04 00:00:00
abstract::SAG (Sensitive to Apoptosis Gene), also known as RBX2 or ROC2, is a RING protein required for the activity of Cullin-RING ligase (CRL). Our recent study showed that Sag total knockout caused embryonic lethality at E11.5-12.5 days with associated defects in vasculogenesis. Whether Sag is required for de novo vasculogen...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.473
更新日期:2014-10-30 00:00:00
abstract::Signet-ring cell carcinoma is classified in poorly differentiated adenocarcinoma with an aggressive nature and a poor prognosis. We have shown that the activation of PI 3-kinase in highly differentiated adenocarcinomas induces loss of cell-cell contact and formation of vacuoles, giving phenotypes similar to those of s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206796
更新日期:2003-08-28 00:00:00
abstract::The nuclear transport receptor importin-β/karyopherin-β1 is overexpressed in cancers that display genomic instability. It is regarded as a promising cancer target and inhibitors are being developed. In addition to its role in nucleo-cytoplasmic transport, importin-β regulates mitosis, but the programmes and pathways i...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0989-x
更新日期:2020-01-01 00:00:00
abstract::A variety of factors cooperate to regulate neovessel formation and persistence. Proangiogenic growth factors have remained an area of intense interest due to their capacity to promote endothelial cell (EC) proliferation and to initiate the angiogenic program. These growth factors are associated with increased cell sur...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207110
更新日期:2003-12-08 00:00:00
abstract::The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.33
更新日期:2010-05-06 00:00:00
abstract::MEK kinases (MEKKs) are serine-threonine kinases that regulate sequential protein phosphorylation pathways involving mitogen-activated protein kinases (MAPKs), including members of the Jun kinase (JNK) family. MEKK1 is a 196 kDa protein that when cleaved by caspase-3-like proteases generates an active COOH-terminal ki...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201421
更新日期:1997-11-13 00:00:00
abstract::Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 is a 220-kDa protein that contains a tandem of two BRCA1 C-Terminal (BRCT) domains. Among missense and nonsense BRCA1 mutations responsible for family breast cancer, some are located into the BRCT tandem ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205915
更新日期:2002-10-03 00:00:00
abstract::Constitutively active HER2/neu activates nuclear factor kappa-B (NF-kappaB) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor-alpha (TNF-alpha). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediate...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207485
更新日期:2004-05-06 00:00:00
abstract::Mdm2 is the major negative regulator of p53 tumor-suppressor activity. This oncoprotein is overexpressed in many human tumors that retain the wild-type p53 allele. As such, targeted inhibition of Mdm2 is being considered as a therapeutic anticancer strategy. The N-terminal hydrophobic pocket of Mdm2 binds to p53 and t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.625
更新日期:2012-11-08 00:00:00
abstract::Osteoclasts are multinuclear bone-resorbing cells that differentiate from hematopoietic precursor cells. Prostate cancer cells frequently spread to bone and secrete soluble signaling factors to accelerate osteoclast differentiation and bone resorption. However, processes and mechanisms that govern the expression of os...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0356-3
更新日期:2018-10-01 00:00:00
abstract::The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis. Although CHK2 activation mechanisms have been amply described, very little is known...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.495
更新日期:2016-08-18 00:00:00