Abstract：
:Although loss of sensitivity to transforming growth factor beta (TGF beta) may be a key step in the escape of epithelial tumours from normal growth control, the intracellular signals determining responsiveness remain controversial, particularly the role of p53. We have investigated this question using thyroid epithelial lines as a model. We analysed (i) human thyroid cancer cell lines having either wild-type (wt) or mutant p53; (ii) rat thyroid lines derived by spontaneous immortalisation following introduction of mutant H-ras, which exhibit high levels of wt p53 but loss of p53-mediated cell-cycle control. Loss of response to TGF beta 1 was found in all human lines bearing mutant p53, and in the majority of the functionally equivalent rat lines, consistent with a role of wt p53 in mediating response. However, introduction of a dominant negative p53 mutant into TGF beta 1 responsive human lines containing wt p53 did not reduce responsiveness, demonstrating that p53 function is not necessary for TGF beta 1 response. On the other hand, expression of a temperature-sensitive (ts) p53 gene in a partially-responsive rat line demonstrated a highly significant modulation of TGF beta response, which fell from 65% inhibition of 3H-thymidine labelling index at 32.5 degrees C (wt p53 conformation) to only 14% at 37.5 degrees C (mutant conformation). The results suggest that p53 and TGF beta generate separate but interacting inhibitory signals, i.e. that p53 modulates but does not mediate TGF beta response. This conclusion explains previous conflicting data and is consistent with current models of cell cycle control by multiple inhibitors of cyclin-dependent kinases.
journal_name
Oncogenejournal_title
Oncogeneauthors
Blaydes JP,Schlumberger M,Wynford-Thomas D,Wyllie FSsubject
Has Abstractpub_date
1995-01-19 00:00:00pages
307-17issue
2eissn
0950-9232issn
1476-5594journal_volume
10pub_type
杂志文章相关文献
ONCOGENE文献大全abstract：:Non-small cell lung carcinomas (NSCLCs) are typically resistant against apoptosis induced by standard chemotherapy. We evaluated the effects of the two potential antitumor agents of the lamellarin class on a highly apoptosis-resistant NSCLC cell line. Both the marine alkaloid lamellarin-D and its synthetic amino deriv...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1210833
更新日期：2008-03-27 00:00:00
abstract：:Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore b...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1209776
更新日期：2007-01-11 00:00:00
abstract：:Histone acetyltransferases (HATs) have a central role in the modification of chromatin as well as in the pathogenesis of a broad set of diseases including cancers. Gcn5 is the first identified transcription-related HAT that has been implicated in the regulation of diverse cellular functions. However, how Gcn5 proteins...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2011.261
更新日期：2012-02-02 00:00:00
abstract：:Lymphoid cells and small intestinal epithelial (SIE) cells are among the most radiosensitive in the body. The factors that account for the differential sensitivity to gamma-radiation among different tissue-types remain poorly understood, but can only partly be explained by differences in rates of cell proliferation. H...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1996-01-04 00:00:00
abstract：:It is presently unclear if ovarian cancers arise through malignant transformation of pre-existing benign tumours. The apparent rarity of loss of heterozygosity (LOH) reported for benign tumours has led to speculation that they lack malignant potential and represent a biological entity distinct from ovarian carcinoma. ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201372
更新日期：1997-10-23 00:00:00
abstract：:Insights into the pathogenesis of human leukemia have relied heavily on studies of the identified chromosomal translocations found in this group of malignant diseases. Acquired, balanced translocations in acute myelogenous leukemia (AML) generally involve transcriptional regulatory genes, whereas in the myeloprolifera...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/sj.onc.1207673
更新日期：2004-05-24 00:00:00
abstract：:Ras-GRF, a guanine-nucleotide exchange factor that activates Ras p21, was tested for its ability to couple to either tyrosine kinase or heterotrimeric G protein signal transduction pathways. Ras-GRF failed to bind the SH2 and SH3 containing adaptor protein Grb2, either in vitro or in vivo. Furthermore, Ras-GRF did not...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1995-05-18 00:00:00
abstract：:Cancer cells lose homeostatic flexibility because of mutations and dysregulated signaling pathways involved in maintaining homeostasis. Tuberous Sclerosis Complex 1 (TSC1) and TSC2 play a fundamental role in cell homeostasis, where signal transduction through TSC1/TSC2 is often compromised in cancer, leading to aberra...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-018-0381-2
更新日期：2018-11-01 00:00:00
abstract：:The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial tran...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2017.259
更新日期：2017-11-23 00:00:00
abstract：:We have previously shown that each of four activated oncogenes (c-myc, neu, ras, and int-2) can serve as transgenic initiators of morphologically distinct adenocarcinomas of the murine mammary gland. Since abnormalities of these oncogenes are found frequently in human breast cancers, such differences are of particular...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:The role of specificity protein 1 (Sp1) in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycyclin...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2011.568
更新日期：2012-08-30 00:00:00
abstract：:Wnt genes encode a set of structurally related cell surface glycoproteins that appear to have roles in cell-cell signalling. The ectopic expression of several murine Wnt genes has been implicated in the transformation of mammary epithelial and the onset of mammary tumours. Wnt11 is expressed in the developing embryo i...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1996-06-20 00:00:00
abstract：:Inhibitor of apoptosis (IAP) proteins are a family comprised of a total of eight mammalian members that were initially described to act as endogenous inhibitors of caspases. In addition, extensive evidence has been accumulated over the last years showing that IAP proteins can regulate various signal transduction pathw...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/onc.2013.63
更新日期：2014-02-06 00:00:00
abstract：:Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell a...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2015.394
更新日期：2016-06-23 00:00:00
abstract：:The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protei...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1210095
更新日期：2007-05-03 00:00:00
abstract：:Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central regio...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1996-07-18 00:00:00
abstract：:The simian double strand DNA tumor virus SV40 encodes the 90-kDa multi-functional protein, large T antigen (LT). LT functions by binding to DNA, as well as to many cellular target proteins such as p53 and retinoblastoma protein (pRB). We report here the identification of a cellular heat shock protein, HSP90, as a prev...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1203475
更新日期：2000-03-09 00:00:00
abstract：:An improved understanding of the biochemical alterations that accompany tumor progression and metastasis is necessary to inform the next generation of diagnostic tools and targeted therapies. Metabolic reprogramming is known to occur during the epithelial-mesenchymal transition (EMT), a process that promotes metastasi...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-019-0885-4
更新日期：2020-04-01 00:00:00
abstract：:Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor, which upon activation, recruits downstream proteins by poly(ADP-ribosyl)ation (PARylation). However, it remains largely unclear how PARP1 activity is regulated. Interestingly, the data obtained through this study revealed that PARP1 was co-immunoprecipitate...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/s41388-018-0506-7
更新日期：2019-02-01 00:00:00
abstract：:We have previously shown (Smith et al., 1994) that antibodies raised against the growth arrest and DNA damage inducible protein Gadd45 co-precipitate proliferating cell nuclear antigen (PCNA), a protein involved in DNA replication and repair. Here we demonstrate that Gadd45 can directly bind to PCNA using a Far-wester...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1995-11-16 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) production by stromal fibroblasts plays an important role in tumor angiogenesis. However, VEGF is also expressed by normal tissue fibroblasts, raising the question of how the VEGF activity of fibroblasts is regulated. Here we report that the latent VEGF angiogenic activity of ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1210535
更新日期：2007-11-08 00:00:00
abstract：:Two thirds of breast cancers express estrogen receptors (ER). ER alpha (ERα) mediates breast cancer cell proliferation, and expression of ERα is the standard choice to indicate adjuvant endocrine therapy. ERbeta (ERβ) inhibits growth in vitro; its effects in vivo have been incompletely investigated and its role in bre...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.261
更新日期：2013-05-09 00:00:00
abstract：:Adhesion to the extracellular matrix (ECM) is critical for epithelial tissue homeostasis and function. ECM detachment induces metabolic stress and programmed cell death via anoikis. ECM-detached mammary epithelial cells are able to rapidly activate autophagy allowing for survival and an opportunity for re-attachment. ...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2012.512
更新日期：2013-10-10 00:00:00
abstract：:Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph-positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic vacuolati...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1201680
更新日期：1998-03-26 00:00:00
abstract：:Damage-associated molecular patterns (DAMPs) are released in response to cell death and stress, and are potent triggers of sterile inflammation. Recent evidence suggests that DAMPs may also have a key role in the development of cancer, as well as in the host response to cytotoxic anti-tumor therapy. As such, DAMPs may...
journal_title：Oncogene
pub_type： 杂志文章,评审
doi：10.1038/onc.2016.104
更新日期：2016-11-17 00:00:00
abstract：:The p53 tumor suppressor protein is frequently mutated in human tumors. It is thought that the p53 pathway is indirectly impaired in the remaining tumors, for example by overexpression of its important regulators Mdm2 and Mdm4, making them attractive targets for the development of anti-cancer agents. Recent studies ha...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/onc.2009.522
更新日期：2010-04-22 00:00:00
abstract：:In this study we have investigated DNA-protein interactions at an AP1-like motif of the neuropeptide tyrosine (NPY) promoter during in vitro differentiation of human neuroblastoma cells SH-SY5Y to mature nonproliferative sympathetic neuron-like cells. These neuroblast-like cells originate from the parental cell line S...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The gfi-1 gene encodes a zinc finger containing protein that is specifically expressed in T-lymphocytes and is a frequent target of proviral insertion in T-cell lymphoma provoked by infection with MoMuLV--a non acute transforming retrovirus. Expression of a gfi-1 transgene targeted to T-cells by the lck proximal promo...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1202191
更新日期：1998-11-19 00:00:00
abstract：:The E2F1 transcription factor, which is deregulated in most human cancers by mutations in the p16-cyclin D-Rb pathway, has both oncogenic and tumor-suppressive properties. This is dramatically illustrated by the phenotype of an E2F1 transgenic mouse model that spontaneously develops tumors in the skin and other epithe...
journal_title：Oncogene
pub_type： 杂志文章
doi：10.1038/sj.onc.1209120
更新日期：2006-02-09 00:00:00
abstract：:Structural rearrangements involving chromosome 13 are frequently seen in B-cell chronic lymphocytic leukaemia. The presence of reciprocal translocations involving 13q14 in 10-15% of cases pinpoints the location of a gene important in leukaemogenesis. In order to characterise the exact location of the 13q14 breakpoint,...
journal_title：Oncogene
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
