Abstract：
:Mutant p53 frequently accumulates in cancer cells and promotes tumor cell invasion, as part of its gain of function. Its accumulation is partially due to enhanced stability, but little is known about how the mRNA levels of mutant p53 can be regulated. Likewise, the impact of cancer therapy on the levels of mutant p53 is poorly understood. We show here that the anthracyclines doxorubicin, daunorubicin and epirubicin further increase the amounts of mutant p53 mRNA and protein in cancer cells. Moreover, we show for the first time that the transcription factor E2F1 associates with the promoter DNA of TP53. Upon genotoxic treatment, E2F1 contributed to the expression of mutant p53, both directly and through induction of TAp73. In contrast, the anthracycline idarubicin and also another topoisomerase inhibitor, etoposide, failed to increase the levels of p53 mRNA, despite their ability to induce the synthesis of TAp73 mRNA. Instead, a natural antisense transcript of TP53, WRAP53, was strongly augmented by idarubicin and etoposide, but only less so by the other anthracyclines under study. RNA corresponding to the first exon of WRAP53 was mainly found in cell nuclei and it reduced the levels of mutant p53. Taken together, this suggests a reciprocal activation pattern of TP53 and WRAP53 by different chemotherapeutics. Reducing the levels of mutant p53 by small-interfering RNA increased chemosensitivity, and idarubicin prevented cell survival more efficiently than the mutant p53-inducing doxorubicin. We conclude that even closely related anthracyclines induce the synthesis of different, opposing transcripts from the TP53 locus. When using these drugs for cancer therapy, the increased levels of mutant p53 may augment its gain of function and thus favor unwanted chemoresistance and tumor progression.
journal_name
Oncogenejournal_title
Oncogeneauthors
Bug M,Dobbelstein Mdoi
10.1038/onc.2011.72subject
Has Abstractpub_date
2011-08-18 00:00:00pages
3612-24issue
33eissn
0950-9232issn
1476-5594pii
onc201172journal_volume
30pub_type
杂志文章相关文献
ONCOGENE文献大全abstract：:Antimicrobial peptides, such as the cathelicidin LL-37/hCAP-18 and its mouse homolog cathelicidin-related antimicrobial peptide (CRAMP), are important effectors of the innate immune system with direct anti-bacterial activity. Cathelicidin is possibly involved in the regulation of tumor cell growth. The aim of this stu...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2013.248
更新日期：2014-05-22 00:00:00
abstract：:The tumor microenvironment plays a critical role in prostate cancer (PC) development and progression. Inappropriate activation of the stroma potentiates the growth and transformation of epithelial tumor cells. Here, we show that upregulation of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-020-1217-4
更新日期：2020-04-01 00:00:00
abstract：:Solid tumors frequently contain hypoxic subregions due to insufficient blood supply. In these domains, cells can undergo p53-dependent apoptosis. Therefore, hypoxia has been implicated as a physiological stimulus for p53 accumulation and activation. In such an environment, p53 mutant cells exhibit a selective growth a...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1207657
更新日期：2004-06-24 00:00:00
abstract：:Constitutive expression of the activated Rap1A protein inhibits differentiation of myogenic C2 cells whereas the inactivated Rap1A protein favours cell differentiation and induces late endocytic compartments clustering. Although the role of Rap1A in MAPK activation has been analysed in various cell types, the signalli...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203984
更新日期：2000-12-07 00:00:00
abstract：:Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of prostaglandins, promotes the development of colorectal cancer, and is a key molecular target of non-steroidal anti-inflammatory drugs, compounds that reduce the relative risk of developing colon cancer. In this study, we showed that interferon gamm...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1210015
更新日期：2007-03-29 00:00:00
abstract：:Lung cancer is the most widely diagnosed malignancy in the world. Understanding early-stage disease will give insight into its pathogenesis. Despite the fact that pre-invasive lesions are challenging to isolate, and often yield insufficient DNA for the analysis of multiple loci, genomic profiling of such lesions will ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1208643
更新日期：2005-07-14 00:00:00
abstract：:In most eukaryotic cells, a link between S and M phases of the cell cycle must be assured in order to maintain the ploidy of newly divided cells. However, in some cell l/pes, e.g. the precursors of platelets megakaryocytes, extra S-phases can occur in the absence of concomitant mitoses, resulting in polyploidy. We hav...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1996-08-15 00:00:00
abstract：:Increasing evidence supports that long noncoding RNAs (lncRNAs) act as master regulators involved in tumorigenesis and development at the N6-methyladenine (m6A) epigenetic modification level. However, the underlying regulatory mechanism in breast cancer (BRCA) remains elusive. Here, we unveil that LINC00942 (LNC942) e...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-020-1338-9
更新日期：2020-07-01 00:00:00
abstract：:The zinc-finger transcription factor Krox24 was analysed for its role in differentiation in P19 embryonal carcinoma cells. Reciprocal dominant negative mutants consisting of Krox24 deleted for a crucial region of the zinc-finger domain (delta Krox24) or of the zinc-finger region alone (delta Krox24Zf) abolished the ac...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1202166
更新日期：1998-11-12 00:00:00
abstract：:Pilocytic astrocytomas (PAs, WHO grade I) are the most common brain tumors in the pediatric and adolescent population, accounting for approximately one-fifth of central nervous system tumors. Because few consistent molecular alterations have been identified in PAs compared to higher grade gliomas, we performed array c...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2008.110
更新日期：2008-08-07 00:00:00
abstract：:Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cel...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201443
更新日期：1997-11-20 00:00:00
abstract：:The translational efficiency of chloramphenicol acetyltransferase (CAT) mRNA containing 5' untranslated region (UTR) sequences of Xenopus c-myc I mRNA was examined in the Xenopus oocyte and early embryo. In contrast to their reduced translation in the oocyte, CAT mRNAs containing 5' UTR sequences located between the c...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC famil...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2011.524
更新日期：2012-08-02 00:00:00
abstract：:By NIH3T3 transfection assay in conjunction with in vitro transient neomycin selection, activated c-H-ras-1 oncogenes were detected in two squamous cell carcinoma cell lines, ZA and HOC-313, newly established from human oral cancer patients. ZA had a point mutational activation at the 13th codon, this activation of c-...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progressio...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:A series of primary human breast tumors was analysed by immunoblotting with anti-neu antibodies. Overproduction of the neu protein-tyrosine kinase, p185neu, was observed in 23 of 56 malignant tumor samples. 29 of these tumors were also immunoblotted with antiphosphotyrosine antibodies. A single prominent phosphotyrosi...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers. As each cell contains many mitochondria with multiple copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a state called heteroplasmy. During cell division, mitochondria are randomly distri...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/sj.onc.1209604
更新日期：2006-08-07 00:00:00
abstract：:To identify genes that are differentially over-expressed in Small Cell Lung Carcinoma (SCLC) we have used a combination of suppression subtractive hybridization and cDNA microarray to analyse the expression profiles of 2400 cDNAs clones. Genes that are over-expressed in SCLC were identified using 32 pairs of fluoresce...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1205480
更新日期：2002-05-23 00:00:00
abstract：:In less than 10 years, the number and importance of non-surgical treatment modalities in patients with colorectal cancer (CRC) have increased dramatically, both in the adjuvant and the advanced settings. However, despite the improvement of cytotoxic therapy in CRC, many patients still develop progressive disease and u...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/sj.onc.1210377
更新日期：2007-05-28 00:00:00
abstract：:Histone deacetylase inhibitors (HDACis) are a promising class of anticancer epigenetic drugs, however, molecular factors influencing the responses of individual tumors to HDACi therapies remain obscure. Here, we sought to identify genes associated with HDACi resistance in gastric cancer. Treating a panel of 17 gastric...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2013.104
更新日期：2014-03-20 00:00:00
abstract：:We have sought to identify and isolate target genes for the zinc finger protein, EVI-1, which has been implicated in the genesis of myelogenous leukemia both in mouse and human. We have approached this with a two-step selection: we first selected for genomic fragments of mouse DNA that bind to the protein with high af...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1202331
更新日期：1998-09-24 00:00:00
abstract：:To gain a more complete understanding of c-myc regulation in chickens, we have completed the structural characterization of the chicken c-myc gene and have begun to investigate c-myc transcription and protein expression. A comparison of c-myc structure and expression between mammals and birds presents an enigma: there...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1996-06-20 00:00:00
abstract：:Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1208817
更新日期：2005-08-25 00:00:00
abstract：:While 25% of human cancers harbor oncogenic Ras mutations, such mutations are not found in astrocytomas. We have previously demonstrated that the activation of receptor tyrosine kinases expressed by malignant human astrocytoma cells and specimens results in functional upregulation of the Ras signalling pathway and inc...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203105
更新日期：1999-12-09 00:00:00
abstract：:Local intravitreal or intra-arterial chemotherapy has improved therapeutic success for the pediatric cancer retinoblastoma (RB), but toxicity remains a major caveat. RB initiates primarily with RB1 loss or, rarely, MYCN amplification, but the critical downstream networks are incompletely understood. We set out to unco...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-020-1372-7
更新日期：2020-07-01 00:00:00
abstract：:Cyclooxygenase-2 (COX-2) is an inducible enzyme that contributes to the generation of chronic inflammation in response to chemical carcinogens and environmental stresses, including ultraviolet B (UVB) irradiation. Although post-translational histone modifications are believed to have an important role in modulating tr...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.71
更新日期：2013-01-24 00:00:00
abstract：:We screened cdc2 kinase inhibitors from cultured mediums of micro organisms using purified mouse cyclin B-cdc2 kinase and a specific substrate peptide for cdc2 kinase. A selective inhibitor of cdc2 kinase was isolated from the cultured medium of Aspergillus species F-25799, and identified as butyrolactone I. Butyrolac...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. Howe...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2017.65
更新日期：2017-08-01 00:00:00
abstract：:Matrix metalloproteinase-2 (MMP-2) has pivotal role in the degradation of extracellular matrix, and thereby enhances the invasive, proliferative and metastatic potential in cancer. Knockdown of MMP-2 using MMP-2 small interfering RNA (pM) in human glioma xenograft cell lines 4910 and 5310 decreased cell proliferation ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.52
更新日期：2013-01-17 00:00:00
abstract：:In previous studies examining the role of pp60c-src in cellular proliferation, we demonstrated that overexpression of wild type (wt) but not mutated c-src in C3H10T1/2 murine embryo fibroblasts resulted in a 2 to 5 fold enhancement of DNA synthesis in response to epidermal growth factor (EGF). Using phosphotyrosine an...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
